Mosaic Copy Number Variation in Human Neurons
We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived...
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| Published in | Science (American Association for the Advancement of Science) Vol. 342; no. 6158; pp. 632 - 637 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Washington, DC
American Association for the Advancement of Science
01.11.2013
The American Association for the Advancement of Science |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0036-8075 1095-9203 1095-9203 |
| DOI | 10.1126/science.1243472 |
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| Abstract | We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 4 1% of neurons have at least one mega base-sea le de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. |
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| AbstractList | We used single cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and post-mortem human brains. We identified aneuploid neurons as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single cell sequencing of endogenous human frontal cortex neurons revealed that 13%-41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic copy number variation is abundant in human neurons. Not All Neurons Are AlikeAs life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al. (p. 632; see the Perspective by Macosko and McCarroll) now show that human neurons also diversify. Neurons taken from postmortem human frontal cortex tissue and neurons derived from induced pluripotent stem cell differentiation in vitro showed surprising diversity in individual cell genomes. Up to 41% of the frontal cortex neurons had copy number variations-no two alike-with deletions more common than duplications. Not All Neurons Are Alike As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al. (p. 632; see the Perspective by Macosko and McCarroll) now show that human neurons also diversify. Neurons taken from postmortem human frontal cortex tissue and neurons derived from induced pluripotent stem cell differentiation in vitro showed surprising diversity in individual cell genomes. Up to 41% of the frontal cortex neurons had copy number variations—no two alike—with deletions more common than duplications. As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al. (p. 632; see the Perspective by Macosko and McCarroll ) now show that human neurons also diversify. Neurons taken from postmortem human frontal cortex tissue and neurons derived from induced pluripotent stem cell differentiation in vitro showed surprising diversity in individual cell genomes. Up to 41% of the frontal cortex neurons had copy number variations--no two alike--with deletions more common than duplications. [PUBLICATION ABSTRACT] We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. [PUBLICATION ABSTRACT] We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 4 1% of neurons have at least one mega base-sea le de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons.We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al. (p. 632 ; see the Perspective by Macosko and McCarroll ) now show that human neurons also diversify. Neurons taken from postmortem human frontal cortex tissue and neurons derived from induced pluripotent stem cell differentiation in vitro showed surprising diversity in individual cell genomes. Up to 41% of the frontal cortex neurons had copy number variations—no two alike—with deletions more common than duplications. Single-cell genomics reveals that individual adult human neurons acquire diverse individual genomes. [Also see Perspective by Macosko and McCarroll ] We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and postmortem human brains. We identified aneuploid neurons, as well as numerous subchromosomal CNVs in euploid neurons. Neurotypic hiPSC-derived neurons had larger CNVs than fibroblasts, and several large deletions were found in hiPSC-derived neurons but not in matched neural progenitor cells. Single-cell sequencing of endogenous human frontal cortex neurons revealed that 13 to 41% of neurons have at least one megabase-scale de novo CNV, that deletions are twice as common as duplications, and that a subset of neurons have highly aberrant genomes marked by multiple alterations. Our results show that mosaic CNV is abundant in human neurons. |
| Author | Lindberg, Michael R. Brennend, Kristen J. Cowing-Zitron, Chris Vermeesch, Joris R. Lasken, Roger S. Gage, Fred H. McConnell, Michael J. Piper, Julia C. Shumilina, Svetlana Voet, Thierry Hall, Ira M. |
| AuthorAffiliation | 1 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037 3 Center for Human Genetics, K.U. Leuven, Leuven, Belgium 8 Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA 22908 6 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093 2 Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute for Biological Studies, La Jolla, CA 92037 5 J. Craig Venter Institute, San Diego, CA 92121 4 Wellcome Trust Sanger Institute, Cambridge, UK 7 Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908 9 Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908 |
| AuthorAffiliation_xml | – name: 9 Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908 – name: 5 J. Craig Venter Institute, San Diego, CA 92121 – name: 4 Wellcome Trust Sanger Institute, Cambridge, UK – name: 1 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037 – name: 2 Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute for Biological Studies, La Jolla, CA 92037 – name: 3 Center for Human Genetics, K.U. Leuven, Leuven, Belgium – name: 7 Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908 – name: 6 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093 – name: 8 Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA 22908 |
| Author_xml | – sequence: 1 givenname: Michael J. surname: McConnell fullname: McConnell, Michael J. – sequence: 2 givenname: Michael R. surname: Lindberg fullname: Lindberg, Michael R. – sequence: 3 givenname: Kristen J. surname: Brennend fullname: Brennend, Kristen J. – sequence: 4 givenname: Julia C. surname: Piper fullname: Piper, Julia C. – sequence: 5 givenname: Thierry surname: Voet fullname: Voet, Thierry – sequence: 6 givenname: Chris surname: Cowing-Zitron fullname: Cowing-Zitron, Chris – sequence: 7 givenname: Svetlana surname: Shumilina fullname: Shumilina, Svetlana – sequence: 8 givenname: Roger S. surname: Lasken fullname: Lasken, Roger S. – sequence: 9 givenname: Joris R. surname: Vermeesch fullname: Vermeesch, Joris R. – sequence: 10 givenname: Ira M. surname: Hall fullname: Hall, Ira M. – sequence: 11 givenname: Fred H. surname: Gage fullname: Gage, Fred H. |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27975276$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/24179226$$D View this record in MEDLINE/PubMed |
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| Snippet | We used single-cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and... As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al.... As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody diversity. McConnell et al.... Not All Neurons Are AlikeAs life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody... Not All Neurons Are Alike As life proceeds, many cells acquire individualized mutations. In the immune system, genome rearrangements generate useful antibody... We used single cell genomic approaches to map DNA copy number variation (CNV) in neurons obtained from human induced pluripotent stem cell (hiPSC) lines and... |
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| SubjectTerms | Aneuploidy antibody diversity Biological and medical sciences Cell differentiation Cell lines Cells Chromosomes DNA Copy Number Variations Fibroblasts frontal lobe Frontal Lobe - cytology Fundamental and applied biological sciences. Psychology genome Genomes Genomics Humans Immune system Individualized Instruction Induced Pluripotent Stem Cells - cytology Male Mosaicism mutation Neural Stem Cells - cytology Neurogenesis Neurons Neurons - cytology Sequence Analysis, DNA Sequence Deletion Sequencing Single-Cell Analysis Somatic cells Stem cells Vertebrates: nervous system and sense organs |
| Title | Mosaic Copy Number Variation in Human Neurons |
| URI | https://www.jstor.org/stable/42620011 https://www.ncbi.nlm.nih.gov/pubmed/24179226 https://www.proquest.com/docview/1447576819 https://www.proquest.com/docview/1448225735 https://www.proquest.com/docview/1660414251 https://www.proquest.com/docview/2000383505 https://pubmed.ncbi.nlm.nih.gov/PMC3975283 |
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