Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells
To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants...
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| Veröffentlicht in: | Cell stem cell 2012-05, Vol.10 (5), p.570-582 |
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| creator | Young, Margaret A. Larson, David E. Sun, Chiao-Wang George, Daniel R. Ding, Li Miller, Christopher A. Lin, Ling Pawlik, Kevin M. Chen, Ken Fan, Xian Schmidt, Heather Kalicki-Veizer, Joelle Cook, Lisa L. Swift, Gary W. Demeter, Ryan T. Wendl, Michael C. Sands, Mark S. Mardis, Elaine R. Wilson, Richard K. Townes, Tim M. Ley, Timothy J. |
| description | To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 shared genetic variants, which could also be detected in rare cells ( |
| doi_str_mv | 10.1016/j.stem.2012.03.002 |
| format | Article |
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► iPSC clones contain hundreds of SNVs that are unique to each clone ► Most iPSC genomes do not contain recurrently mutated genes or pathways ► Reprogramming can select for rare cells with shared genetic variants ► Most SNVs are probably preexisting mutations “captured” by cloning</description><identifier>ISSN: 1934-5909</identifier><identifier>EISSN: 1875-9777</identifier><identifier>DOI: 10.1016/j.stem.2012.03.002</identifier><identifier>PMID: 22542160</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cell Differentiation ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Cell Proliferation ; Clone Cells ; DNA - analysis ; DNA - genetics ; Fundamental and applied biological sciences. Psychology ; Genomic Instability ; Guided Tissue Regeneration - methods ; Guided Tissue Regeneration - standards ; Induced Pluripotent Stem Cells - metabolism ; Induced Pluripotent Stem Cells - pathology ; Mice ; Molecular and cellular biology ; Mutation ; Polymorphism, Single Nucleotide ; Regenerative Medicine</subject><ispartof>Cell stem cell, 2012-05, Vol.10 (5), p.570-582</ispartof><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>2012 ll Press. All rights reserved. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-22c0c3b661354a09f060d97596d57e585f389d7f64194a05116084d7837c89cf3</citedby><cites>FETCH-LOGICAL-c584t-22c0c3b661354a09f060d97596d57e585f389d7f64194a05116084d7837c89cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1934590912001191$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25913719$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22542160$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Young, Margaret A.</creatorcontrib><creatorcontrib>Larson, David E.</creatorcontrib><creatorcontrib>Sun, Chiao-Wang</creatorcontrib><creatorcontrib>George, Daniel R.</creatorcontrib><creatorcontrib>Ding, Li</creatorcontrib><creatorcontrib>Miller, Christopher A.</creatorcontrib><creatorcontrib>Lin, Ling</creatorcontrib><creatorcontrib>Pawlik, Kevin M.</creatorcontrib><creatorcontrib>Chen, Ken</creatorcontrib><creatorcontrib>Fan, Xian</creatorcontrib><creatorcontrib>Schmidt, Heather</creatorcontrib><creatorcontrib>Kalicki-Veizer, Joelle</creatorcontrib><creatorcontrib>Cook, Lisa L.</creatorcontrib><creatorcontrib>Swift, Gary W.</creatorcontrib><creatorcontrib>Demeter, Ryan T.</creatorcontrib><creatorcontrib>Wendl, Michael C.</creatorcontrib><creatorcontrib>Sands, Mark S.</creatorcontrib><creatorcontrib>Mardis, Elaine R.</creatorcontrib><creatorcontrib>Wilson, Richard K.</creatorcontrib><creatorcontrib>Townes, Tim M.</creatorcontrib><creatorcontrib>Ley, Timothy J.</creatorcontrib><title>Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells</title><title>Cell stem cell</title><addtitle>Cell Stem Cell</addtitle><description>To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 shared genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool. These data suggest that most of the genetic variation in iPSC clones is not caused by reprogramming per se, but is rather a consequence of cloning individual cells, which “captures” their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.
► iPSC clones contain hundreds of SNVs that are unique to each clone ► Most iPSC genomes do not contain recurrently mutated genes or pathways ► Reprogramming can select for rare cells with shared genetic variants ► Most SNVs are probably preexisting mutations “captured” by cloning</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cell Proliferation</subject><subject>Clone Cells</subject><subject>DNA - analysis</subject><subject>DNA - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genomic Instability</subject><subject>Guided Tissue Regeneration - methods</subject><subject>Guided Tissue Regeneration - standards</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Induced Pluripotent Stem Cells - pathology</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Mutation</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Regenerative Medicine</subject><issn>1934-5909</issn><issn>1875-9777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkl9rFDEUxYMotq5-AR8kL0JfZsyfyWQCItRF20KLBfU5pJk726yzyZpkFvrtm2HXqi-lT0m4v3s4954g9JaSmhLafljXKcOmZoSymvCaEPYMHdNOikpJKZ-Xu-JNJRRRR-hVSmtChKREvkRHjImG0ZYco91nY3-tYph8j6-mbLILPmHn8bWJ4LMZ8RLGMeFTawuT8RAivgop4zDgfAv4DDxkZ_E5ZIhhVV4u383FC99PFnp8PU7RbUMuYvh7sbvXe41eDGZM8OZwLtDPr19-LM-ry29nF8vTy8qKrskVY5ZYftO2lIvGEDWQlvRKCtX2QoLoxMA71cuhbagqdUHLTF3Ty45L2yk78AX6tNfdTjcb6G1xEc2ot9FtTLzTwTj9f8W7W70KO8150zWMF4GTg0AMvydIWW9csmUE4yFMSVNSQKKY6p6AUiq4FHJWZXvUxpBShOHBESUz1-q1nrPVc7aacF2yLU3v_p3loeVPmAV4fwBMsmYcovHWpb-cUJTL8icW6OOeg7L5nYOok3XgS1ougs26D-4xH_fUeMK_</recordid><startdate>20120504</startdate><enddate>20120504</enddate><creator>Young, Margaret A.</creator><creator>Larson, David E.</creator><creator>Sun, Chiao-Wang</creator><creator>George, Daniel R.</creator><creator>Ding, Li</creator><creator>Miller, Christopher A.</creator><creator>Lin, Ling</creator><creator>Pawlik, Kevin M.</creator><creator>Chen, Ken</creator><creator>Fan, Xian</creator><creator>Schmidt, Heather</creator><creator>Kalicki-Veizer, Joelle</creator><creator>Cook, Lisa L.</creator><creator>Swift, Gary W.</creator><creator>Demeter, Ryan T.</creator><creator>Wendl, Michael C.</creator><creator>Sands, Mark S.</creator><creator>Mardis, Elaine R.</creator><creator>Wilson, Richard K.</creator><creator>Townes, Tim M.</creator><creator>Ley, Timothy J.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20120504</creationdate><title>Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells</title><author>Young, Margaret A. ; Larson, David E. ; Sun, Chiao-Wang ; George, Daniel R. ; Ding, Li ; Miller, Christopher A. ; Lin, Ling ; Pawlik, Kevin M. ; Chen, Ken ; Fan, Xian ; Schmidt, Heather ; Kalicki-Veizer, Joelle ; Cook, Lisa L. ; Swift, Gary W. ; Demeter, Ryan T. ; Wendl, Michael C. ; Sands, Mark S. ; Mardis, Elaine R. ; Wilson, Richard K. ; Townes, Tim M. ; Ley, Timothy J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c584t-22c0c3b661354a09f060d97596d57e585f389d7f64194a05116084d7837c89cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Differentiation</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cell Proliferation</topic><topic>Clone Cells</topic><topic>DNA - analysis</topic><topic>DNA - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genomic Instability</topic><topic>Guided Tissue Regeneration - methods</topic><topic>Guided Tissue Regeneration - standards</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Induced Pluripotent Stem Cells - pathology</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Mutation</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Regenerative Medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Young, Margaret A.</creatorcontrib><creatorcontrib>Larson, David E.</creatorcontrib><creatorcontrib>Sun, Chiao-Wang</creatorcontrib><creatorcontrib>George, Daniel R.</creatorcontrib><creatorcontrib>Ding, Li</creatorcontrib><creatorcontrib>Miller, Christopher A.</creatorcontrib><creatorcontrib>Lin, Ling</creatorcontrib><creatorcontrib>Pawlik, Kevin M.</creatorcontrib><creatorcontrib>Chen, Ken</creatorcontrib><creatorcontrib>Fan, Xian</creatorcontrib><creatorcontrib>Schmidt, Heather</creatorcontrib><creatorcontrib>Kalicki-Veizer, Joelle</creatorcontrib><creatorcontrib>Cook, Lisa L.</creatorcontrib><creatorcontrib>Swift, Gary W.</creatorcontrib><creatorcontrib>Demeter, Ryan T.</creatorcontrib><creatorcontrib>Wendl, Michael C.</creatorcontrib><creatorcontrib>Sands, Mark S.</creatorcontrib><creatorcontrib>Mardis, Elaine R.</creatorcontrib><creatorcontrib>Wilson, Richard K.</creatorcontrib><creatorcontrib>Townes, Tim M.</creatorcontrib><creatorcontrib>Ley, Timothy J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell stem cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Young, Margaret A.</au><au>Larson, David E.</au><au>Sun, Chiao-Wang</au><au>George, Daniel R.</au><au>Ding, Li</au><au>Miller, Christopher A.</au><au>Lin, Ling</au><au>Pawlik, Kevin M.</au><au>Chen, Ken</au><au>Fan, Xian</au><au>Schmidt, Heather</au><au>Kalicki-Veizer, Joelle</au><au>Cook, Lisa L.</au><au>Swift, Gary W.</au><au>Demeter, Ryan T.</au><au>Wendl, Michael C.</au><au>Sands, Mark S.</au><au>Mardis, Elaine R.</au><au>Wilson, Richard K.</au><au>Townes, Tim M.</au><au>Ley, Timothy J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells</atitle><jtitle>Cell stem cell</jtitle><addtitle>Cell Stem Cell</addtitle><date>2012-05-04</date><risdate>2012</risdate><volume>10</volume><issue>5</issue><spage>570</spage><epage>582</epage><pages>570-582</pages><issn>1934-5909</issn><eissn>1875-9777</eissn><abstract>To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 shared genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool. These data suggest that most of the genetic variation in iPSC clones is not caused by reprogramming per se, but is rather a consequence of cloning individual cells, which “captures” their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.
► iPSC clones contain hundreds of SNVs that are unique to each clone ► Most iPSC genomes do not contain recurrently mutated genes or pathways ► Reprogramming can select for rare cells with shared genetic variants ► Most SNVs are probably preexisting mutations “captured” by cloning</abstract><cop>Cambridge, MA</cop><pub>Elsevier Inc</pub><pmid>22542160</pmid><doi>10.1016/j.stem.2012.03.002</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Cell Differentiation Cell differentiation, maturation, development, hematopoiesis Cell physiology Cell Proliferation Clone Cells DNA - analysis DNA - genetics Fundamental and applied biological sciences. Psychology Genomic Instability Guided Tissue Regeneration - methods Guided Tissue Regeneration - standards Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Mice Molecular and cellular biology Mutation Polymorphism, Single Nucleotide Regenerative Medicine |
| title | Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells |
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