Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells
A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we de...
Saved in:
| Published in | eLife Vol. 6 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
eLife Sciences Publications Ltd
30.01.2017
eLife Sciences Publication eLife Sciences Publications, Ltd |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2050-084X 2050-084X |
| DOI | 10.7554/eLife.19406 |
Cover
Loading…
| Abstract | A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes (
DLG2, KCNE4, PTRF, HTR2C
,
CAMKV
) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions.
Common medications can disturb the electrical signals that cause the heart to beat, potentially resulting in sudden death. Many of the drugs that have these “cardiotoxic” effects were not designed to affect the heart, and include anti-allergenics and anti-vomiting drugs. In general, only a small proportion of individuals treated with these drugs will be at risk of fatal side effects; this risk variation is thought to be due to genetic differences. If these people could be reliably identified, the drugs could be used to treat others who will not develop cardiotoxic reactions, but it is difficult to predict the effect a drug will have on the beating of the heart.
Stillitano, Hansen et al. have now investigated whether skin cells can be used to predict an individual’s likelihood of developing cardiotoxic side effects. Skin cells can be reprogrammed to form pluripotent stem cells, which have the ability to develop into any of the cell types in the adult body – including heart muscle cells. The effects of drugs could then be tested on these artificially created heart cells, yet it is not clear whether these effects would be the same as those seen in actual heart cells
Stillitano, Hansen et al. created heart cells from skin samples collected from many different people and treated the cells with a drug that affects the rhythm of the heart. Some of the cells came from people whose heart rhythm is strongly affected by the drug, and others came from people whose heart rhythm is barely altered. The response of the lab-grown cells was closely related to whether the cells came from a person who was susceptible to the effects of the drug. Further investigation revealed that the genes that are important for maintaining a regular heartbeat differ in people who experience strong cardiotoxic side effects from those that do not.
Overall, the results presented by Stillitano, Hansen et al. support the idea that induced pluripotent stem cells could be used to predict an individual’s risk of developing cardiotoxic reactions. Further work is now needed to develop this approach. |
|---|---|
| AbstractList | A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes (DLG2, KCNE4, PTRF, HTR2C, CAMKV) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions. A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes ( DLG2, KCNE4, PTRF, HTR2C , CAMKV ) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions. DOI: http://dx.doi.org/10.7554/eLife.19406.001 Common medications can disturb the electrical signals that cause the heart to beat, potentially resulting in sudden death. Many of the drugs that have these “cardiotoxic” effects were not designed to affect the heart, and include anti-allergenics and anti-vomiting drugs. In general, only a small proportion of individuals treated with these drugs will be at risk of fatal side effects; this risk variation is thought to be due to genetic differences. If these people could be reliably identified, the drugs could be used to treat others who will not develop cardiotoxic reactions, but it is difficult to predict the effect a drug will have on the beating of the heart. Stillitano, Hansen et al. have now investigated whether skin cells can be used to predict an individual’s likelihood of developing cardiotoxic side effects. Skin cells can be reprogrammed to form pluripotent stem cells, which have the ability to develop into any of the cell types in the adult body – including heart muscle cells. The effects of drugs could then be tested on these artificially created heart cells, yet it is not clear whether these effects would be the same as those seen in actual heart cells Stillitano, Hansen et al. created heart cells from skin samples collected from many different people and treated the cells with a drug that affects the rhythm of the heart. Some of the cells came from people whose heart rhythm is strongly affected by the drug, and others came from people whose heart rhythm is barely altered. The response of the lab-grown cells was closely related to whether the cells came from a person who was susceptible to the effects of the drug. Further investigation revealed that the genes that are important for maintaining a regular heartbeat differ in people who experience strong cardiotoxic side effects from those that do not. Overall, the results presented by Stillitano, Hansen et al. support the idea that induced pluripotent stem cells could be used to predict an individual’s risk of developing cardiotoxic reactions. Further work is now needed to develop this approach. DOI: http://dx.doi.org/10.7554/eLife.19406.002 A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes (DLG2, KCNE4, PTRF, HTR2C, CAMKV) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions.A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes (DLG2, KCNE4, PTRF, HTR2C, CAMKV) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions. A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes ( , ) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions. A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes ( DLG2, KCNE4, PTRF, HTR2C , CAMKV ) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions. Common medications can disturb the electrical signals that cause the heart to beat, potentially resulting in sudden death. Many of the drugs that have these “cardiotoxic” effects were not designed to affect the heart, and include anti-allergenics and anti-vomiting drugs. In general, only a small proportion of individuals treated with these drugs will be at risk of fatal side effects; this risk variation is thought to be due to genetic differences. If these people could be reliably identified, the drugs could be used to treat others who will not develop cardiotoxic reactions, but it is difficult to predict the effect a drug will have on the beating of the heart. Stillitano, Hansen et al. have now investigated whether skin cells can be used to predict an individual’s likelihood of developing cardiotoxic side effects. Skin cells can be reprogrammed to form pluripotent stem cells, which have the ability to develop into any of the cell types in the adult body – including heart muscle cells. The effects of drugs could then be tested on these artificially created heart cells, yet it is not clear whether these effects would be the same as those seen in actual heart cells Stillitano, Hansen et al. created heart cells from skin samples collected from many different people and treated the cells with a drug that affects the rhythm of the heart. Some of the cells came from people whose heart rhythm is strongly affected by the drug, and others came from people whose heart rhythm is barely altered. The response of the lab-grown cells was closely related to whether the cells came from a person who was susceptible to the effects of the drug. Further investigation revealed that the genes that are important for maintaining a regular heartbeat differ in people who experience strong cardiotoxic side effects from those that do not. Overall, the results presented by Stillitano, Hansen et al. support the idea that induced pluripotent stem cells could be used to predict an individual’s risk of developing cardiotoxic reactions. Further work is now needed to develop this approach. A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is however challenging as it usually develops in some genetically predisposed individuals with normal cardiac repolarization at baseline. Here, we describe a platform based on a genetically diverse panel of induced pluripotent stem cells (iPSCs) that reproduces susceptibility to develop a cardiotoxic drug response. We generated iPSC-derived cardiomyocytes from patients presenting in vivo with extremely low or high changes in cardiac repolarization in response to a pharmacological challenge with sotalol. In vitro, the responses to sotalol were highly variable but strongly correlated to the inter-individual differences observed in vivo. Transcriptomic profiling identified dysregulation of genes (DLG2, KCNE4, PTRF, HTR2C, CAMKV) involved in downstream regulation of cardiac repolarization machinery as underlying high sensitivity to sotalol. Our findings offer novel insights for the development of iPSC-based screening assays for testing individual drug reactions.DOI: http://dx.doi.org/10.7554/eLife.19406.001 |
| Author | Karakikes, Ioannis Desseaux, Carole Funck-Brentano, Christian Iyengar, Ravi Jeziorowska, Dorota Li, Ronald Hansen, Jens Kong, Chi-Wing Valogne, Yannick Hajjar, Roger J Scott, Stuart Hulot, Jean-Sébastien Zahr, Noël Geng, Lin Wu, Ma Salem, Joe-Elie Stillitano, Francesca Reynier, Stephan |
| Author_xml | – sequence: 1 givenname: Francesca surname: Stillitano fullname: Stillitano, Francesca organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 2 givenname: Jens surname: Hansen fullname: Hansen, Jens organization: Department of Pharmacology and Systems Therapeutics, Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 3 givenname: Chi-Wing surname: Kong fullname: Kong, Chi-Wing organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 4 givenname: Ioannis surname: Karakikes fullname: Karakikes, Ioannis organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 5 givenname: Christian surname: Funck-Brentano fullname: Funck-Brentano, Christian organization: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, INSERM, CIC-1421, Institute of Cardiometabolism and Nutrition, Paris, France – sequence: 6 givenname: Lin surname: Geng fullname: Geng, Lin organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 7 givenname: Stuart surname: Scott fullname: Scott, Stuart organization: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 8 givenname: Stephan surname: Reynier fullname: Reynier, Stephan organization: Cellectis Stem Cells, Paris, France – sequence: 9 givenname: Ma surname: Wu fullname: Wu, Ma organization: Cellectis Stem Cells, Paris, France – sequence: 10 givenname: Yannick surname: Valogne fullname: Valogne, Yannick organization: Cellectis Stem Cells, Paris, France – sequence: 11 givenname: Carole surname: Desseaux fullname: Desseaux, Carole organization: Cellectis Stem Cells, Paris, France – sequence: 12 givenname: Joe-Elie surname: Salem fullname: Salem, Joe-Elie organization: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, INSERM, CIC-1421, Institute of Cardiometabolism and Nutrition, Paris, France – sequence: 13 givenname: Dorota surname: Jeziorowska fullname: Jeziorowska, Dorota organization: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, INSERM, CIC-1421, Institute of Cardiometabolism and Nutrition, Paris, France – sequence: 14 givenname: Noël surname: Zahr fullname: Zahr, Noël organization: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, INSERM, CIC-1421, Institute of Cardiometabolism and Nutrition, Paris, France – sequence: 15 givenname: Ronald surname: Li fullname: Li, Ronald organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States, Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Stockholm, Sweden, Dr. Li Dak-Sum Centre, The University of Hong Kong – Karolinska Institutet Collaboration in Regenerative Medicine, Pokfulam, Hong Kong – sequence: 16 givenname: Ravi surname: Iyengar fullname: Iyengar, Ravi organization: Department of Pharmacology and Systems Therapeutics, Systems Biology Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 17 givenname: Roger J surname: Hajjar fullname: Hajjar, Roger J organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States – sequence: 18 givenname: Jean-Sébastien orcidid: 0000-0001-5463-6117 surname: Hulot fullname: Hulot, Jean-Sébastien organization: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, United States, Sorbonne Universités, UPMC Univ Paris 06, AP-HP, INSERM, CIC-1421, Institute of Cardiometabolism and Nutrition, Paris, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28134617$$D View this record in MEDLINE/PubMed https://hal.sorbonne-universite.fr/hal-01484452$$DView record in HAL |
| BookMark | eNptUl1rFDEUHaRia-2T7xLwRZGp-ZzJvAilqC2siFDBt5DP3SzZyZhkKv33Zne70hbzkuTmnHNzD-dlczTG0TbNawTPe8boR7vwzp6jgcLuWXOCIYMt5PTX0YPzcXOW8xrW1VPO0fCiOcYcEdqh_qSJ36KxwY9LkOes7VS88sGXO1AiMGletn40s7YGhFgxP27AH19WQIJJjjaA6CpNra0ubZ6s9s5rcCBMYU5-isWOBeRiN0DbEPKr5rmTIduz-_20-fnl883lVbv4_vX68mLRagaH0rKOKIl4p3tiEbO6jqqQwchqDh0mqMeOUS2tNlJqCg1iijuidD9ASonj5LS53uuaKNdiSn4j052I0otdIaalkKl4Hawgivecsk5hSSm1Shk3GEIodmh71VXr015rmtXGGl0nSjI8En38MvqVWMZbwXA_DJRUgfd7gdUT2tXFQmxrEFFOKcO3qGLf3TdL8fdscxEbn7fWVcPjnEU1BQ-k57ir0LdPoOs4p7HaKtDACBw4J6yi3jz8_b_-hwxUANoDdIo5J-uE9kUWH7fD-CAQFNuoiV3UxC5qlfPhCecg-z_0Xzl11hc |
| CitedBy_id | crossref_primary_10_1093_braincomms_fcab271 crossref_primary_10_1186_s13287_023_03502_5 crossref_primary_10_1016_j_vascn_2018_09_002 crossref_primary_10_1089_neur_2023_0023 crossref_primary_10_1126_sciadv_abn6579 crossref_primary_10_1111_cts_12674 crossref_primary_10_1177_2472555218775028 crossref_primary_10_1093_cvr_cvad143 crossref_primary_10_1039_D3NA00727H crossref_primary_10_1242_dmm_030320 crossref_primary_10_1093_cvr_cvab201 crossref_primary_10_3389_fnmol_2023_1183315 crossref_primary_10_1161_CIRCRESAHA_117_311080 crossref_primary_10_3390_ph14060525 crossref_primary_10_3390_cells10092335 crossref_primary_10_1161_ATVBAHA_120_314695 crossref_primary_10_1002_stem_3110 crossref_primary_10_1093_eurheartj_ehab007 crossref_primary_10_3390_bioengineering10020237 crossref_primary_10_1016_j_actbio_2019_05_016 crossref_primary_10_1016_j_stemcr_2024_08_005 crossref_primary_10_1080_17460441_2020_1736031 crossref_primary_10_1093_cvr_cvz024 crossref_primary_10_1016_j_toxlet_2018_01_001 crossref_primary_10_1038_s41467_021_27856_7 crossref_primary_10_1161_CIRCRESAHA_119_315209 crossref_primary_10_3389_fncel_2021_626192 crossref_primary_10_1016_j_coisb_2017_05_006 crossref_primary_10_1016_j_pharmthera_2018_04_009 crossref_primary_10_1016_j_stem_2017_06_005 crossref_primary_10_1007_s00204_021_03172_3 crossref_primary_10_1016_j_stemcr_2018_04_006 crossref_primary_10_1093_cvr_cvab115 crossref_primary_10_1109_JTEHM_2019_2907945 crossref_primary_10_1007_s12265_022_10298_x crossref_primary_10_1016_j_chembiol_2021_02_016 crossref_primary_10_1016_j_cotox_2020_04_001 crossref_primary_10_1152_physrev_00039_2017 crossref_primary_10_1172_jci_insight_127652 crossref_primary_10_1016_j_jacc_2018_05_004 crossref_primary_10_1161_ATVBAHA_121_316464 crossref_primary_10_3390_biomedicines11020334 crossref_primary_10_1007_s10557_017_6735_0 crossref_primary_10_7554_eLife_24276 crossref_primary_10_1161_CIRCRESAHA_117_310965 crossref_primary_10_1161_CIRCRESAHA_119_315378 crossref_primary_10_1097_FJC_0000000000000972 crossref_primary_10_3390_ijms18061173 crossref_primary_10_1161_HCG_0000000000000043 crossref_primary_10_1093_toxsci_kfae079 crossref_primary_10_1038_s41467_019_13868_x crossref_primary_10_1177_2472630318803277 crossref_primary_10_1063_5_0160677 crossref_primary_10_3389_fcell_2022_855763 crossref_primary_10_1038_s41598_025_88946_w crossref_primary_10_1016_j_mcp_2024_101965 crossref_primary_10_1016_j_vascn_2022_107184 crossref_primary_10_1242_bio_052381 crossref_primary_10_1093_cvr_cvae042 crossref_primary_10_1016_j_yrtph_2020_104756 crossref_primary_10_1093_toxsci_kfaa010 crossref_primary_10_3103_S0735272722090047 crossref_primary_10_1161_CIRCULATIONAHA_123_063917 crossref_primary_10_1161_CIRCRESAHA_118_311209 crossref_primary_10_3390_ijms22147667 crossref_primary_10_1111_bph_15757 crossref_primary_10_1007_s11886_023_01852_3 |
| Cites_doi | 10.1074/jbc.M400285200 10.1016/j.pharmthera.2010.08.008 10.1186/1471-2164-12-293 10.1016/j.jacc.2014.04.057 10.1161/CIRCULATIONAHA.108.798918 10.1038/nmeth.1923 10.1089/scd.2012.0490 10.1016/0002-9149(90)90207-H 10.2174/157488610789869148 10.1161/CIRCULATIONAHA.112.001216 10.1007/s00109-003-0522-z 10.1038/ncb0709-789 10.1093/bioinformatics/btr625 10.1038/nrd1108 10.1038/ng.362 10.1016/j.cell.2014.10.050 10.1093/eurheartj/ehs351 10.1186/1471-2105-14-128 10.1001/jama.1993.03510210076031 10.1093/bioinformatics/btp120 10.1001/jama.296.15.1858 10.1016/j.ahj.2013.11.004 10.1161/01.CIR.0000014448.19052.4C 10.1126/scisignal.2000723 10.1161/CIRCULATIONAHA.112.000570 10.1038/clpt.2011.38 10.2174/157488610789869166 10.1093/eurheartj/ehr082 10.5966/sctm.2013-0110 10.1093/europace/eut214 10.1371/journal.pgen.1000874 10.1016/0002-9149(93)90035-B 10.1124/pr.110.003723 10.1161/CIRCULATIONAHA.113.001883 10.1038/nmeth.2999 10.1113/jphysiol.2010.191395 10.1096/fj.13-228007 10.1111/j.1365-2796.2005.01589.x 10.1016/j.pharmthera.2014.03.004 10.1371/journal.pone.0132459 10.1371/journal.pone.0026397 10.1038/nature09747 10.1111/bcp.12208 10.1038/nbt.1621 10.1056/NEJMoa0908679 10.1016/j.hrthm.2014.06.023 10.1007/s12265-012-9416-1 10.1111/bcp.12201 10.1016/j.cardiores.2005.11.013 10.1038/bjp.2008.238 10.1016/j.taap.2014.04.007 10.1016/S0195-668X(03)00436-6 10.1517/17425255.2015.981523 10.1085/jgp.201210899 10.1038/nrg2779 10.1016/j.hrthm.2004.10.039 |
| ContentType | Journal Article |
| Copyright | 2017, Stillitano et al. This work is licensed under the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/3.0/ ) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Attribution 2017, Stillitano et al 2017 Stillitano et al |
| Copyright_xml | – notice: 2017, Stillitano et al. This work is licensed under the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/3.0/ ) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Attribution – notice: 2017, Stillitano et al 2017 Stillitano et al |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 3V. 7X7 7XB 88E 88I 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FYUFA GHDGH GNUQQ HCIFZ K9. LK8 M0S M1P M2P M7P PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS Q9U 7X8 1XC VOOES 5PM DOA |
| DOI | 10.7554/eLife.19406 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Central (Corporate) Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Science Database (Alumni Edition) ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials - QC Biological Science Collection ProQuest Central Natural Science Collection ProQuest One ProQuest Central Korea Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Biological Sciences ProQuest Health & Medical Collection Medical Database Science Database Biological Science Database ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China ProQuest Central Basic MEDLINE - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access) PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Science Journals (Alumni Edition) ProQuest Biological Science Collection ProQuest Central Basic ProQuest Science Journals ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE CrossRef Publicly Available Content Database |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 4 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology Medicine |
| EISSN | 2050-084X |
| ExternalDocumentID | oai_doaj_org_article_3b878456b2a444ebbdf9d3342f144ebc PMC5279943 oai_HAL_hal_01484452v1 28134617 10_7554_eLife_19406 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHGRI NIH HHS grantid: U54 HG008098 – fundername: NIGMS NIH HHS grantid: P50 GM071558 – fundername: NIGMS NIH HHS grantid: R01 GM054508 – fundername: ; grantid: Research subvention – fundername: ; grantid: U54 HG008098 – fundername: ; grantid: P50 GM071558 – fundername: ; grantid: GM54508 |
| GroupedDBID | 53G 5VS 7X7 88E 88I 8FE 8FH 8FI 8FJ AAFWJ AAKDD AAYXX ABUWG ACGFO ACGOD ACPRK ADBBV ADRAZ AENEX AFKRA AFPKN ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BBNVY BCNDV BENPR BHPHI BPHCQ BVXVI CCPQU CITATION DIK DWQXO EMOBN FYUFA GNUQQ GROUPED_DOAJ GX1 HCIFZ HMCUK HYE IAO IEA IHR INH INR ISR ITC KQ8 LK8 M1P M2P M48 M7P M~E NQS OK1 PGMZT PHGZM PHGZT PIMPY PQQKQ PROAC PSQYO RHI RNS RPM UKHRP CGR CUY CVF ECM EIF NPM PJZUB PPXIY PQGLB 3V. 7XB 8FK K9. PKEHL PQEST PQUKI PRINS Q9U 7X8 1XC VOOES 5PM PUEGO |
| ID | FETCH-LOGICAL-c509t-563ba186c73e15ec554b1d21ec80f23172f54caecdaac40d15b8f3bc790443f83 |
| IEDL.DBID | M48 |
| ISSN | 2050-084X |
| IngestDate | Wed Aug 27 01:32:08 EDT 2025 Thu Aug 21 14:32:43 EDT 2025 Fri May 09 12:12:50 EDT 2025 Thu Aug 07 15:10:46 EDT 2025 Sat Aug 23 14:30:13 EDT 2025 Mon Jul 21 05:35:54 EDT 2025 Tue Jul 01 01:12:02 EDT 2025 Thu Apr 24 22:55:49 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | human biology cardiotoxicity induced pluripotent stem cells medicine human arrhythmia |
| Language | English |
| License | Attribution: http://creativecommons.org/licenses/by This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c509t-563ba186c73e15ec554b1d21ec80f23172f54caecdaac40d15b8f3bc790443f83 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work. |
| ORCID | 0000-0001-5463-6117 0000-0001-7682-5613 0000-0002-0331-3307 0000-0003-0406-5189 |
| OpenAccessLink | https://doaj.org/article/3b878456b2a444ebbdf9d3342f144ebc |
| PMID | 28134617 |
| PQID | 1953098835 |
| PQPubID | 2045579 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_3b878456b2a444ebbdf9d3342f144ebc pubmedcentral_primary_oai_pubmedcentral_nih_gov_5279943 hal_primary_oai_HAL_hal_01484452v1 proquest_miscellaneous_1862937826 proquest_journals_1953098835 pubmed_primary_28134617 crossref_citationtrail_10_7554_eLife_19406 crossref_primary_10_7554_eLife_19406 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2017-01-30 |
| PublicationDateYYYYMMDD | 2017-01-30 |
| PublicationDate_xml | – month: 01 year: 2017 text: 2017-01-30 day: 30 |
| PublicationDecade | 2010 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England – name: Cambridge |
| PublicationTitle | eLife |
| PublicationTitleAlternate | Elife |
| PublicationYear | 2017 |
| Publisher | eLife Sciences Publications Ltd eLife Sciences Publication eLife Sciences Publications, Ltd |
| Publisher_xml | – name: eLife Sciences Publications Ltd – name: eLife Sciences Publication – name: eLife Sciences Publications, Ltd |
| References | Kannankeril (bib19) 2005; 2 Leonoudakis (bib23) 2004; 279 Trapnell (bib53) 2009; 25 Inoue (bib16) 2011; 89 Mann (bib30) 2015; 11 Terrenoire (bib52) 2013; 141 Chen (bib7) 2012; 28 Budnitz (bib3) 2006; 296 Darpo (bib10) 2014; 77 Itzhaki (bib17) 2011; 471 Liu (bib26) 2015; 10 Lundy (bib27) 2013; 22 Keller (bib21) 2010; 5 Petropoulou (bib39) 2014; 77 Zanetti (bib58) 1993; 12 Roden (bib44) 2008; 118 Wang (bib56) 2014; 64 Berger (bib2) 2010; 3 Burridge (bib4) 2014; 11 Levy (bib24) 2010; 588 Kannankeril (bib18) 2010; 62 Paulussen (bib38) 2004; 82 Liang (bib25) 2013; 127 Sinnecker (bib49) 2013; 6 Makkar (bib29) 1993; 270 Pfeufer (bib40) 2009; 41 Roden (bib43) 2008; 154 Roden (bib42) 2006; 259 Sinnecker (bib50) 2014; 143 Cerrone (bib5) 2011; 32 Sager (bib46) 2014; 167 Hulot (bib15) 2003; 24 Karakikes (bib20) 2014; 3 Fermini (bib11) 2003; 2 Trapnell (bib54) 2010; 28 Moretti (bib32) 2010; 363 Schaaf (bib48) 2011; 6 Nozaki (bib36) 2014; 278 Yang (bib57) 2002; 105 Giorgi (bib14) 2010; 5 Rajab (bib41) 2010; 6 Maguy (bib28) 2006; 69 Behr (bib1) 2013; 34 Funck-Brentano (bib12) 1993; 72 Langmead (bib22) 2012; 9 Odening (bib37) 2014; 11 Nabi (bib34) 2009; 11 Gintant (bib13) 2011; 129 Moss (bib33) 1992; 85 Rolland (bib45) 2014; 159 McIntyre (bib31) 2011; 12 Crotti (bib9) 2013; 127 Sarganas (bib47) 2014; 16 Chen (bib6) 2013; 14 Soyka (bib51) 1990; 65 Cirulli (bib8) 2010; 11 Turnbull (bib55) 2014; 28 Navarrete (bib35) 2013; 128 28134615 - Elife. 2017 Jan 30;6:e24276. doi: 10.7554/eLife.24276 |
| References_xml | – volume: 279 start-page: 22331 year: 2004 ident: bib23 article-title: Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins publication-title: Journal of Biological Chemistry doi: 10.1074/jbc.M400285200 – volume: 129 start-page: 109 year: 2011 ident: bib13 article-title: An evaluation of hERG current assay performance: Translating preclinical safety studies to clinical QT prolongation publication-title: Pharmacology & Therapeutics doi: 10.1016/j.pharmthera.2010.08.008 – volume: 12 start-page: 293 year: 2011 ident: bib31 article-title: RNA-seq: technical variability and sampling publication-title: BMC Genomics doi: 10.1186/1471-2164-12-293 – volume: 64 start-page: 451 year: 2014 ident: bib56 article-title: Genome editing of isogenic human induced pluripotent stem cells recapitulates long QT phenotype for drug testing publication-title: Journal of the American College of Cardiology doi: 10.1016/j.jacc.2014.04.057 – volume: 118 start-page: 981 year: 2008 ident: bib44 article-title: Repolarization reserve: a moving target publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.108.798918 – volume: 9 start-page: 357 year: 2012 ident: bib22 article-title: Fast gapped-read alignment with Bowtie 2 publication-title: Nature Methods doi: 10.1038/nmeth.1923 – volume: 22 start-page: 1991 year: 2013 ident: bib27 article-title: Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells publication-title: Stem Cells and Development doi: 10.1089/scd.2012.0490 – volume: 65 start-page: 74A year: 1990 ident: bib51 article-title: Clinical safety profile of sotalol in patients with arrhythmias publication-title: The American Journal of Cardiology doi: 10.1016/0002-9149(90)90207-H – volume: 5 start-page: 54 year: 2010 ident: bib14 article-title: QT interval prolongation: preclinical and clinical testing arrhythmogenesis in drugs and regulatory implications publication-title: Current Drug Safety doi: 10.2174/157488610789869148 – volume: 127 start-page: 1009 year: 2013 ident: bib9 article-title: Calmodulin mutations associated with recurrent cardiac arrest in infants publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.112.001216 – volume: 82 start-page: 182 year: 2004 ident: bib38 article-title: Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients publication-title: Journal of Molecular Medicine doi: 10.1007/s00109-003-0522-z – volume: 11 start-page: 789 year: 2009 ident: bib34 article-title: Cavin fever: regulating caveolae publication-title: Nature Cell Biology doi: 10.1038/ncb0709-789 – volume: 28 start-page: 105 year: 2012 ident: bib7 article-title: Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers publication-title: Bioinformatics doi: 10.1093/bioinformatics/btr625 – volume: 2 start-page: 439 year: 2003 ident: bib11 article-title: The impact of drug-induced QT interval prolongation on drug discovery and development publication-title: Nature Reviews Drug Discovery doi: 10.1038/nrd1108 – volume: 41 start-page: 407 year: 2009 ident: bib40 article-title: Common variants at ten loci modulate the QT interval duration in the QTSCD Study publication-title: Nature Genetics doi: 10.1038/ng.362 – volume: 159 start-page: 1212 year: 2014 ident: bib45 article-title: A proteome-scale map of the human interactome network publication-title: Cell doi: 10.1016/j.cell.2014.10.050 – volume: 34 start-page: 89 year: 2013 ident: bib1 article-title: Drug-induced arrhythmia: pharmacogenomic prescribing? publication-title: European Heart Journal doi: 10.1093/eurheartj/ehs351 – volume: 14 year: 2013 ident: bib6 article-title: Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool publication-title: BMC Bioinformatics doi: 10.1186/1471-2105-14-128 – volume: 270 start-page: 2590 year: 1993 ident: bib29 article-title: Female Gender as a Risk Factor for Torsades de Pointes Associated With Cardiovascular Drugs publication-title: JAMA doi: 10.1001/jama.1993.03510210076031 – volume: 25 start-page: 1105 year: 2009 ident: bib53 article-title: TopHat: discovering splice junctions with RNA-Seq publication-title: Bioinformatics doi: 10.1093/bioinformatics/btp120 – volume: 296 start-page: 1858 year: 2006 ident: bib3 article-title: National surveillance of emergency department visits for outpatient adverse drug events publication-title: JAMA doi: 10.1001/jama.296.15.1858 – volume: 167 start-page: 292 year: 2014 ident: bib46 article-title: Rechanneling the cardiac proarrhythmia safety paradigm: a meeting report from the Cardiac Safety Research Consortium publication-title: American Heart Journal doi: 10.1016/j.ahj.2013.11.004 – volume: 105 start-page: 1943 year: 2002 ident: bib57 article-title: Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes publication-title: Circulation doi: 10.1161/01.CIR.0000014448.19052.4C – volume: 3 year: 2010 ident: bib2 article-title: Systems pharmacology of arrhythmias publication-title: Science Signaling doi: 10.1126/scisignal.2000723 – volume: 128 start-page: S3 year: 2013 ident: bib35 article-title: Screening drug-induced arrhythmia [corrected] using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.112.000570 – volume: 89 start-page: 655 year: 2011 ident: bib16 article-title: The use of induced pluripotent stem cells in drug development publication-title: Clinical Pharmacology & Therapeutics doi: 10.1038/clpt.2011.38 – volume: 5 start-page: 73 year: 2010 ident: bib21 article-title: Prokinetic agents and QT prolongation: a familiar scene with new actors publication-title: Current Drug Safety doi: 10.2174/157488610789869166 – volume: 32 start-page: 2109 year: 2011 ident: bib5 article-title: Genetics of sudden death: focus on inherited channelopathies publication-title: European Heart Journal doi: 10.1093/eurheartj/ehr082 – volume: 3 start-page: 18 year: 2014 ident: bib20 article-title: Small molecule-mediated directed differentiation of human embryonic stem cells toward ventricular cardiomyocytes publication-title: Stem Cells Translational Medicine doi: 10.5966/sctm.2013-0110 – volume: 16 start-page: 101 year: 2014 ident: bib47 article-title: Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany publication-title: Europace doi: 10.1093/europace/eut214 – volume: 6 year: 2010 ident: bib41 article-title: Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations publication-title: PLoS Genetics doi: 10.1371/journal.pgen.1000874 – volume: 72 start-page: 17B year: 1993 ident: bib12 article-title: Rate-corrected QT interval: techniques and limitations publication-title: The American Journal of Cardiology doi: 10.1016/0002-9149(93)90035-B – volume: 62 start-page: 760 year: 2010 ident: bib18 article-title: Drug-induced long QT syndrome publication-title: Pharmacological Reviews doi: 10.1124/pr.110.003723 – volume: 127 start-page: 1677 year: 2013 ident: bib25 article-title: Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.113.001883 – volume: 11 start-page: 855 year: 2014 ident: bib4 article-title: Chemically defined generation of human cardiomyocytes publication-title: Nature Methods doi: 10.1038/nmeth.2999 – volume: 588 start-page: 2657 year: 2010 ident: bib24 article-title: The membrane protein MiRP3 regulates Kv4.2 channels in a KChIP-dependent manner publication-title: The Journal of Physiology doi: 10.1113/jphysiol.2010.191395 – volume: 28 start-page: 644 year: 2014 ident: bib55 article-title: Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium publication-title: The FASEB Journal doi: 10.1096/fj.13-228007 – volume: 259 start-page: 59 year: 2006 ident: bib42 article-title: Long QT syndrome: reduced repolarization reserve and the genetic link publication-title: Journal of Internal Medicine doi: 10.1111/j.1365-2796.2005.01589.x – volume: 143 start-page: 246 year: 2014 ident: bib50 article-title: Induced pluripotent stem cell-derived cardiomyocytes for drug development and toxicity testing publication-title: Pharmacology & Therapeutics doi: 10.1016/j.pharmthera.2014.03.004 – volume: 10 year: 2015 ident: bib26 article-title: Common Variants in TRDN and CALM1 Are Associated with Risk of Sudden Cardiac Death in Chronic Heart Failure Patients in Chinese Han Population publication-title: PLOS One doi: 10.1371/journal.pone.0132459 – volume: 6 year: 2011 ident: bib48 article-title: Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology publication-title: PLoS One doi: 10.1371/journal.pone.0026397 – volume: 471 start-page: 225 year: 2011 ident: bib17 article-title: Modelling the long QT syndrome with induced pluripotent stem cells publication-title: Nature doi: 10.1038/nature09747 – volume: 77 start-page: 618 year: 2014 ident: bib39 article-title: The genetics of pro-arrhythmic adverse drug reactions publication-title: British Journal of Clinical Pharmacology doi: 10.1111/bcp.12208 – volume: 28 start-page: 511 year: 2010 ident: bib54 article-title: Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation publication-title: Nature Biotechnology doi: 10.1038/nbt.1621 – volume: 363 start-page: 1397 year: 2010 ident: bib32 article-title: Patient-specific induced pluripotent stem-cell models for long-QT syndrome publication-title: New England Journal of Medicine doi: 10.1056/NEJMoa0908679 – volume: 11 start-page: 2107 year: 2014 ident: bib37 article-title: How do sex hormones modify arrhythmogenesis in long QT syndrome? Sex hormone effects on arrhythmogenic substrate and triggered activity publication-title: Heart Rhythm doi: 10.1016/j.hrthm.2014.06.023 – volume: 6 start-page: 31 year: 2013 ident: bib49 article-title: Modeling long-QT syndromes with iPS cells publication-title: Journal of Cardiovascular Translational Research doi: 10.1007/s12265-012-9416-1 – volume: 77 start-page: 522 year: 2014 ident: bib10 article-title: Are women more susceptible than men to drug-induced QT prolongation? Concentration-QTc modelling in a phase 1 study with oral rac-sotalol publication-title: British Journal of Clinical Pharmacology doi: 10.1111/bcp.12201 – volume: 69 start-page: 798 year: 2006 ident: bib28 article-title: Involvement of lipid rafts and caveolae in cardiac ion channel function publication-title: Cardiovascular Research doi: 10.1016/j.cardiores.2005.11.013 – volume: 154 start-page: 1502 year: 2008 ident: bib43 article-title: Cellular basis of drug-induced torsades de pointes publication-title: British Journal of Pharmacology doi: 10.1038/bjp.2008.238 – volume: 278 start-page: 72 year: 2014 ident: bib36 article-title: Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation publication-title: Toxicology and Applied Pharmacology doi: 10.1016/j.taap.2014.04.007 – volume: 85 start-page: I140 year: 1992 ident: bib33 article-title: Clinical features of the idiopathic long QT syndrome publication-title: Circulation – volume: 24 start-page: 1663 year: 2003 ident: bib15 article-title: Influence of endogenous oestrogens on QT interval duration publication-title: European Heart Journal doi: 10.1016/S0195-668X(03)00436-6 – volume: 11 start-page: 1 year: 2015 ident: bib30 article-title: Human induced pluripotent stem cell-derived hepatocytes for toxicology testing publication-title: Expert Opinion on Drug Metabolism & Toxicology doi: 10.1517/17425255.2015.981523 – volume: 141 start-page: 61 year: 2013 ident: bib52 article-title: Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics publication-title: The Journal of General Physiology doi: 10.1085/jgp.201210899 – volume: 11 start-page: 415 year: 2010 ident: bib8 article-title: Uncovering the roles of rare variants in common disease through whole-genome sequencing publication-title: Nature Reviews Genetics doi: 10.1038/nrg2779 – volume: 2 start-page: 134 year: 2005 ident: bib19 article-title: Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relatives publication-title: Heart Rhythm doi: 10.1016/j.hrthm.2004.10.039 – volume: 12 start-page: 883 year: 1993 ident: bib58 article-title: Sotalol: a new class III antiarrhythmic agent publication-title: Clinical Pharmacy – reference: 28134615 - Elife. 2017 Jan 30;6:e24276. doi: 10.7554/eLife.24276 |
| SSID | ssj0000748819 |
| Score | 2.437084 |
| Snippet | A large number of drugs can induce prolongation of cardiac repolarization and life-threatening cardiac arrhythmias. The prediction of this side effect is... |
| SourceID | doaj pubmedcentral hal proquest pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| SubjectTerms | Anti-Arrhythmia Agents - metabolism arrhythmia Arrhythmias, Cardiac - chemically induced Cardiac arrhythmia Cardiomyocytes cardiotoxicity Cardiotoxins - metabolism Drug dosages Gene Expression Profiling Genes Heart Heart diseases Human Biology and Medicine Humans induced pluripotent stem cells Induced Pluripotent Stem Cells - drug effects Induced Pluripotent Stem Cells - physiology Life Sciences Mass Screening - methods Medicine Models, Biological Mutation Pluripotency Research Subjects Stem cells |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1La9wwEBYlEOilNE0fTtOilpwKbqyXJR-T0rCUtFBIIDdhvZrAsg5Zu5B_nxnZu-y2hV5ytD2SzXwjzcOjGUKOau9caKMv61Y1pUwhlk4mU7q6MSY6cEBy-7bvP-rZpfx2pa42Wn1hTthYHnhk3LFwRhvQ8o63UsoIM6cmCCF5YnjpcfcFnbfhTOU9WINgsmY8kKdBZR7H85sUP4PLjr2NNlRQrtQPiuUa8yD_NjL_zJXcUD5nz8mzyWqkJ-PX7pEncfGC7I59JO_3SYcdzfBcOV0Oy5ynklNe72nf0XA3_CrB8QYIA513QPPzgmL0lbYUdoI4p12CYQ7jMSWeu8TcIboacDsfYFfpwLDuKZZ8phjoX74kl2dfL77MyqmTQunBIOhLVQvXMlN7LSJT0QNDHAucRW-qBBae5klJD5CFtvWyCkw5k4TzuqmkFMmIV2Rn0S3iG0KZ1LwOKnJEMhrjtAe4NUve6ZYlXpBPK-ZaP5UZx24XcwvuBiJhMxI2I1GQozXx7Vhd499kp4jSmgRLYucbICh2EhT7P0EpyEfAeGuO2cm5xXsYVZVS8d-sIIcrEbDTYl5a_NNYgegKVZAP68ewDJHlAFQ3AA14hmDpgbNWkNejxKxfxQ0TEizFgugtWdr6lu0ni5vrXOpbcd00Uhw8BgPekqccbZIKA46HZKe_G-I7sKh69z4vngcyqyND priority: 102 providerName: Directory of Open Access Journals – databaseName: Health & Medical Collection dbid: 7X7 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3da9RAEF-0ovRFtGqNVlmlT0Js9iu7eZIqlkNaQWjh3kL2qy0cl_OSFPrfO5PkYk_FxySzSdjf7s5vZmdnCDnMnbW-Ci7NK1WkMvqQWhlNavPCmGDBAOnLt519z2cX8ttczUeHWzOGVW7WxH6h9rVDH_kRbvdk0F6oT6ufKVaNwt3VsYTGffIAU5dhSJee68nHAurRgMYbjuVpUJxH4fQ6ho9guGOFozuKqM_XD-rlCqMh_6aaf0ZM3lFBJ0_I45E70uMB7KfkXljukYdDNcnbPfLobNwnf0ZqLHGGB81p0zV94EofA3tL25r6dXeZgiUOmHq6qEHmxzlFdyytKCwNYUHrCM0sOmhSPIiJwUR002C16GCZqYFptxRzQFP0_DfPycXJ1_Mvs3QsrZA6YAhtqnJhK2Zyp0VgKjjoG8s8Z8GZLALl0zwq6QBDX1VOZp4pa6KwTheZlCIa8YLsLOtleEkok5rnXgWO0AZjrHaAv2bRWV2xyBPyYdPPpRvzjmP5i0UJ9geCUvaglD0oCTmchFdDuo1_i31GwCYRzJHd36jXl-U45UphjTbADy2vpJQBxmQsvBCSR4aXLiHvAe6td8yOT0u8h25WKRW_YQk52IyGcpzdTfl7LCbk3fQY5iV2OQBVdyADpiJQP7DeErI_DJ7pU9wwIYE6JkRvDautf9l-sry-6nN_K66LQopX__-t12SXI_3I0Ld4QHbadRfeAHlq7dt-hvwCLf8dmw priority: 102 providerName: ProQuest |
| Title | Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/28134617 https://www.proquest.com/docview/1953098835 https://www.proquest.com/docview/1862937826 https://hal.sorbonne-universite.fr/hal-01484452 https://pubmed.ncbi.nlm.nih.gov/PMC5279943 https://doaj.org/article/3b878456b2a444ebbdf9d3342f144ebc |
| Volume | 6 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3da9wwDDddy2AvY9_L1h3e6NMgt_grdp5GO1qO0ZZt9ODeQuzYbeG4dPdRev_9JCc5dl0f9phEToIlWT_JskTIQe6srSvv0rxSRSpD7VMrg0ltXhjjLTggsX3b2Xk-GsvvEzXZIX0zzm4CFw-6dthPajyfDu9-r7-CwgN-HWqwhl_86XXwQ_DGsfT2HpgkjRp61uH8uCRrkNPY5INnKtYynbRn9e6P37JOsYg_2JwrTJH8F3_eT6P8yy6dPCNPO0BJD1sJeE52_OwFedy2mFy_JA02O8Mj53SxWsQUlpgNu6bLhtbz1WUKPjlwt6bTBmh-XlAMzNKKwiLhp7QJMMxiqCbFI5mYVkT7ATfTFSw4DWDuJcVq0BT3ABavyPjk-OLbKO2aLKQOsMIyVbmwFTO508Iz5R1MiGU1Z96ZLAD40zwo6YCbdVU5mdVMWROEdbrIpBTBiNdkd9bM_FtCmdQ8r5XnyGRvjNUOJEGz4KyuWOAJ-dxPbum6CuTYCGNagieCnCgjJ8rIiYQcbIhv2sIbD5MdIZc2JFgtO95o5pdlp3ylsEYbQIqWV1JKD9IZiloIyQPDS5eQT8DjrXeMDk9LvIcBVykVv2UJ2e9FoOzFtMRNyAykWqiEfNw8Bg3FKQdGNSugAacRQCD4cQl500rM5lPcMCEBRCZEb8nS1r9sP5ldX8Uq4IrropDi3X989z15whGNZBhq3Ce7y_nKfwAstbQD8khP9IDsHR2f__g1iBGJQdSdP5DuJEc |
| linkProvider | Scholars Portal |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtR1db9Mw8DQ68fGCYHwFBhg0XpDC6o8kzgNCG2zqWFsB6qS9hdixt0lVU_oB6p_iN3KXpGUFxNseY58dy3e-L5_vAHZia0yROxvGeZSGyhcuNMrr0MSp1s6gAVKVb-v1486J-nganW7Az-VbGAqrXPLEilEXpSUf-S5d97RxvIzejb-FVDWKbleXJTRqsjh2ix9osk3fHn1A_L4S4vBg8L4TNlUFQovCcRZGsTQ517FNpOORsyhPDS8Ed1a3PWo7ifCRsrj8Is-tahc8MtpLY5O0rZT0WuK812BTSTRlWrC5f9D_9GXl1UGBrFHG1g8BE5x613UvvHvDU0U1lS6JvqpCAAq0c4q__Fu5_TNG85LQO7wDtxttle3V5HUXNtxoC67X9SsXW3Cj19zM34OSiqrR03Y2nU-rUJkq6nbBZiUrJvOzEG1_pKKCDUuE-Txg5ABmOUNm5Ias9DjMkEsopKefFL7ElgPGwzkythJ1-xmjrNOM7hqm9-HkSrb9AbRG5cg9AsZVIuIicoKIyWltEosUl3BvTZJzLwJ4vdznzDaZzqngxjBDi4eQklVIySqkBLCzAh7XCT7-DbZPCFuBUFbuqqGcnGXNIc-k0YlGjdSIXCnl8BT4tJBSCc_p0wbwEtG9Nkdnr5tRGzl2lYrEdx7A9pIasoafTLPf1B_Ai1U3cgLackRUOUcYNE5R2UR7MYCHNfGsfiU0lwqV1QCSNbJaW8t6z-jivMo2HokkTZV8_P9lPYebnUGvm3WP-sdP4JYg5adNns1taM0mc_cUVbeZedacFwZfr_qI_gL7V1w6 |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtR3ZbtNAcFWKqHhBUC5DgQWVFyST7GHv-gGhQolSmlYgtVLfXO_VRorikAOUX-PrmPERGkC89dH27NreuWdnZwjZTa0xrvA2Toski2VwPjYy6NikmdbegANStW87Ok77p_LzWXK2QX62Z2EwrbKViZWgdqXFGHkHt3u6MF4kndCkRXzZ772ffIuxgxTutLbtNGoSOfTLH-C-zd4d7AOuX3Pe-3TysR83HQZiC4pyHiepMAXTqVXCs8Rb0K2GOc681d0Alo_iIZEWfsUVhZVdxxKjgzBWZV0pRdAC5r1BbiqRMOQxdaZW8R1QzRq0bX0kUMHEHT8YBv-WZRK7K11RglWvAFBtl5iJ-beZ-2e25hX117tL7jR2K92rCe0e2fDjbXKr7mS53CZbR80e_X1SYns1POROZ4tZlTRT5d8u6bykbrq4iIdjB_Tk6KgEmK8nFEPBtKAglvyIlgGGGQwOxXgIFBOZaDtgMlqAiCvByp9TrD9Ncddh9oCcXsuiPySb43LsHxPKpOKpSzxHsvJaG2WB9hQL1qiCBR6RN-0657apeY6tN0Y5-D6IlLxCSl4hJSK7K-BJXerj32AfEGErEKzPXd0opxd5w-65MFppsE0NL6SUHvghZE4IyQPDSxuRV4DutTn6e4Mc72GIV8qEf2cR2WmpIW8kyyz_zQcRebl6DDIBlxwQVS4ABtxUMDvBc4zIo5p4Vq_imgkJZmtE1BpZrX3L-pPx8LKqO55wlWVSPPn_Z70gW8CY-eDg-PApuc3RCupiiHOHbM6nC_8MbLi5eV4xCyXn182dvwASnF8K |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Modeling+susceptibility+to+drug-induced+long+QT+with+a+panel+of+subject-specific+induced+pluripotent+stem+cells&rft.jtitle=eLife&rft.au=Stillitano%2C+Francesca&rft.au=Hansen%2C+Jens&rft.au=Kong%2C+Chi-Wing&rft.au=Karakikes%2C+Ioannis&rft.date=2017-01-30&rft.issn=2050-084X&rft.eissn=2050-084X&rft.volume=6&rft_id=info:doi/10.7554%2FeLife.19406&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2050-084X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2050-084X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2050-084X&client=summon |