An in vivo RNAi screen uncovers the role of AdoR signaling and adenosine deaminase in controlling intestinal stem cell activity
Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity i...
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| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 1; pp. 464 - 471 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
07.01.2020
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| Online Access | Get full text |
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| Abstract | Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor (AdoR) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A (Adgf-A) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation. |
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| AbstractList | Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor (AdoR) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A (Adgf-A) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation. Regulation of stem cells by microenvironment signals is important to maintain epithelial homeostasis. Using a quantitative readout, we screened for receptor genes that affect the intestinal stem cell pool size in the adult Drosophila midgut. The top candidate of our screen, AdoR , underscores the importance of purinergic signaling in controlling ISC activity. Furthermore, we identified a pivotal role of an enterocyte-derived metabolic enzyme, Adgf-A, in limiting the activity of extracellular adenosine and shaping the ISC microenvironment. Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor ( AdoR ) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A ( Adgf-A ) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation. Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the midgut, we identified ( ) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of ( ) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation. Significance Regulation of stem cells by microenvironment signals is important to maintain epithelial homeostasis. Using a quantitative readout, we screened for receptor genes that affect the intestinal stem cell pool size in the adult Drosophila midgut. The top candidate of our screen, AdoR , underscores the importance of purinergic signaling in controlling ISC activity. Furthermore, we identified a pivotal role of an enterocyte-derived metabolic enzyme, Adgf-A, in limiting the activity of extracellular adenosine and shaping the ISC microenvironment. Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in the Drosophila midgut, we identified adenosine receptor ( AdoR ) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation of adenosine deaminase-related growth factor A ( Adgf-A ) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. As Adgf-A expression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation. |
| Author | Bosch, Justin A. Villalta, Christians He, Xi Franklin, Brian Hu, Yanhui Xu, Chiwei Perrimon, Norbert Ramos, Justine Tang, Hong-Wen Regimbald-Dumas, Yannik |
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| Cites_doi | 10.1002/ibd.21898 10.1016/j.yexcr.2011.07.020 10.1016/j.bbamcr.2004.03.005 10.1038/ncb2804 10.1038/nature04333 10.1111/j.1748-1716.2009.01957.x 10.1016/S0300-9084(86)80177-8 10.1158/1078-0432.CCR-03-0651 10.1371/journal.pgen.1001297 10.1126/science.1136606 10.1007/s00109-012-0990-0 10.1038/nature07329 10.1016/j.lfs.2016.10.008 10.1242/jeb.01529 10.1073/pnas.1019736108 10.1093/nar/gkv1097 10.1016/j.cub.2015.02.019 10.1172/JCI200524009 10.1016/j.celrep.2014.08.052 10.1016/j.stem.2012.06.017 10.1016/j.stem.2010.11.026 10.1016/j.cell.2009.05.014 10.1038/nrc3613 10.1016/j.celrep.2015.01.051 10.1016/j.cub.2005.07.010 10.3389/fncel.2014.00321 10.1189/jlb.1109764 10.1016/S0378-1119(01)00762-4 10.1073/pnas.1109348108 10.1038/nature16170 10.1016/j.ibmb.2006.12.003 10.1534/genetics.113.160713 10.1038/nature04371 10.1007/s11248-005-1174-2 10.1038/sj.bjp.0706429 10.1016/j.ydbio.2013.01.032 10.7554/eLife.00886 10.1083/jcb.201211160 10.1126/science.277.5329.1103 10.7554/eLife.22441 10.1016/S0896-6273(00)80736-9 10.1074/jbc.M113.484212 10.1073/pnas.062059699 10.14348/molcells.2016.0014 10.1038/emboj.2012.248 10.1038/nature08822 10.1016/j.celrep.2018.12.079 10.1038/nbt1210-1248 10.1016/j.stem.2008.10.016 10.1074/jbc.M112.378018 10.1038/nrd2638 10.15252/embj.201591517 10.1016/j.cell.2011.11.041 |
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| Keywords | adenosine receptor RNAi screen intestinal stem cell adenosine deaminase |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: C.X. and N.P. designed research; C.X., B.F., H.-W.T., Y.R.-D., and J.R. performed research; J.A.B. and C.V. contributed new reagents/analytic tools; C.X., Y.R.-D., Y.H., X.H., and N.P. analyzed data; and C.X. and N.P. wrote the paper. Reviewers: U.B., University of California, Los Angeles; and H.J., Buck Institute for Research on Aging. Contributed by Norbert Perrimon, November 15, 2019 (sent for review January 9, 2019; reviewed by Utpal Bannerjee and Heinrich Jasper) |
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| References | e_1_3_3_50_2 e_1_3_3_16_2 e_1_3_3_18_2 e_1_3_3_39_2 e_1_3_3_12_2 e_1_3_3_37_2 e_1_3_3_14_2 e_1_3_3_35_2 e_1_3_3_33_2 e_1_3_3_54_2 e_1_3_3_10_2 e_1_3_3_31_2 e_1_3_3_52_2 e_1_3_3_40_2 e_1_3_3_5_2 e_1_3_3_7_2 e_1_3_3_9_2 e_1_3_3_27_2 e_1_3_3_29_2 e_1_3_3_23_2 e_1_3_3_48_2 e_1_3_3_25_2 e_1_3_3_46_2 e_1_3_3_1_2 Pignata S. (e_1_3_3_42_2) 1994; 5 e_1_3_3_44_2 e_1_3_3_3_2 e_1_3_3_21_2 e_1_3_3_51_2 e_1_3_3_17_2 e_1_3_3_19_2 e_1_3_3_38_2 e_1_3_3_13_2 e_1_3_3_36_2 e_1_3_3_15_2 e_1_3_3_34_2 e_1_3_3_32_2 e_1_3_3_11_2 e_1_3_3_30_2 e_1_3_3_53_2 e_1_3_3_6_2 e_1_3_3_8_2 e_1_3_3_28_2 e_1_3_3_49_2 e_1_3_3_24_2 e_1_3_3_47_2 e_1_3_3_26_2 e_1_3_3_45_2 e_1_3_3_2_2 e_1_3_3_20_2 e_1_3_3_43_2 e_1_3_3_4_2 e_1_3_3_22_2 e_1_3_3_41_2 |
| References_xml | – ident: e_1_3_3_43_2 doi: 10.1002/ibd.21898 – ident: e_1_3_3_3_2 doi: 10.1016/j.yexcr.2011.07.020 – ident: e_1_3_3_44_2 doi: 10.1016/j.bbamcr.2004.03.005 – ident: e_1_3_3_14_2 doi: 10.1038/ncb2804 – volume: 5 start-page: 967 year: 1994 ident: e_1_3_3_42_2 article-title: The enterocyte-like differentiation of the Caco-2 tumor cell line strongly correlates with responsiveness to cAMP and activation of kinase A pathway publication-title: Cell Growth Differ. contributor: fullname: Pignata S. – ident: e_1_3_3_1_2 doi: 10.1038/nature04333 – ident: e_1_3_3_40_2 doi: 10.1111/j.1748-1716.2009.01957.x – ident: e_1_3_3_36_2 doi: 10.1016/S0300-9084(86)80177-8 – ident: e_1_3_3_48_2 doi: 10.1158/1078-0432.CCR-03-0651 – ident: e_1_3_3_18_2 doi: 10.1371/journal.pgen.1001297 – ident: e_1_3_3_21_2 doi: 10.1126/science.1136606 – ident: e_1_3_3_51_2 doi: 10.1007/s00109-012-0990-0 – ident: e_1_3_3_8_2 doi: 10.1038/nature07329 – ident: e_1_3_3_47_2 doi: 10.1016/j.lfs.2016.10.008 – ident: e_1_3_3_15_2 doi: 10.1242/jeb.01529 – ident: e_1_3_3_39_2 doi: 10.1073/pnas.1019736108 – ident: e_1_3_3_37_2 doi: 10.1093/nar/gkv1097 – ident: e_1_3_3_19_2 doi: 10.1016/j.cub.2015.02.019 – ident: e_1_3_3_35_2 doi: 10.1172/JCI200524009 – ident: e_1_3_3_17_2 doi: 10.1016/j.celrep.2014.08.052 – ident: e_1_3_3_10_2 doi: 10.1016/j.stem.2012.06.017 – ident: e_1_3_3_5_2 doi: 10.1016/j.stem.2010.11.026 – ident: e_1_3_3_7_2 doi: 10.1016/j.cell.2009.05.014 – ident: e_1_3_3_23_2 doi: 10.1038/nrc3613 – ident: e_1_3_3_12_2 doi: 10.1016/j.celrep.2015.01.051 – ident: e_1_3_3_24_2 doi: 10.1016/j.cub.2005.07.010 – ident: e_1_3_3_45_2 doi: 10.3389/fncel.2014.00321 – ident: e_1_3_3_50_2 doi: 10.1189/jlb.1109764 – ident: e_1_3_3_32_2 doi: 10.1016/S0378-1119(01)00762-4 – ident: e_1_3_3_6_2 doi: 10.1073/pnas.1109348108 – ident: e_1_3_3_30_2 doi: 10.1038/nature16170 – ident: e_1_3_3_22_2 doi: 10.1016/j.ibmb.2006.12.003 – ident: e_1_3_3_54_2 doi: 10.1534/genetics.113.160713 – ident: e_1_3_3_2_2 doi: 10.1038/nature04371 – ident: e_1_3_3_53_2 doi: 10.1007/s11248-005-1174-2 – ident: e_1_3_3_33_2 doi: 10.1038/sj.bjp.0706429 – ident: e_1_3_3_11_2 doi: 10.1016/j.ydbio.2013.01.032 – ident: e_1_3_3_20_2 doi: 10.7554/eLife.00886 – ident: e_1_3_3_13_2 doi: 10.1083/jcb.201211160 – ident: e_1_3_3_29_2 doi: 10.1126/science.277.5329.1103 – ident: e_1_3_3_31_2 doi: 10.7554/eLife.22441 – ident: e_1_3_3_26_2 doi: 10.1016/S0896-6273(00)80736-9 – ident: e_1_3_3_34_2 doi: 10.1074/jbc.M113.484212 – ident: e_1_3_3_41_2 doi: 10.1073/pnas.062059699 – ident: e_1_3_3_16_2 doi: 10.14348/molcells.2016.0014 – ident: e_1_3_3_9_2 doi: 10.1038/emboj.2012.248 – ident: e_1_3_3_52_2 doi: 10.1038/nature08822 – ident: e_1_3_3_28_2 doi: 10.1016/j.celrep.2018.12.079 – ident: e_1_3_3_38_2 doi: 10.1038/nbt1210-1248 – ident: e_1_3_3_4_2 doi: 10.1016/j.stem.2008.10.016 – ident: e_1_3_3_46_2 doi: 10.1074/jbc.M112.378018 – ident: e_1_3_3_49_2 doi: 10.1038/nrd2638 – ident: e_1_3_3_27_2 doi: 10.15252/embj.201591517 – ident: e_1_3_3_25_2 doi: 10.1016/j.cell.2011.11.041 |
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| Snippet | Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their... Significance Regulation of stem cells by microenvironment signals is important to maintain epithelial homeostasis. Using a quantitative readout, we screened... Regulation of stem cells by microenvironment signals is important to maintain epithelial homeostasis. Using a quantitative readout, we screened for receptor... |
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| SubjectTerms | Adenosine Adenosine - metabolism Adenosine deaminase Adenosine Deaminase - metabolism Animals Animals, Genetically Modified Biological Sciences Cell Differentiation Cell Proliferation Damage Down-Regulation Downstream effects Drosophila Drosophila Proteins - genetics Drosophila Proteins - metabolism Enterocytes Enterocytes - physiology Enzymatic activity Fruit flies Gene expression Gene Knock-In Techniques Gene Knockdown Techniques Growth factors Intestine Kinases MAP kinase MAP Kinase Signaling System - genetics Metabolites Midgut Multipotent Stem Cells - physiology Protein kinase A Ras protein Receptors, Purinergic P1 - genetics Receptors, Purinergic P1 - metabolism RNA Interference RNA-mediated interference Signaling Stem cells |
| Title | An in vivo RNAi screen uncovers the role of AdoR signaling and adenosine deaminase in controlling intestinal stem cell activity |
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