Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells

详细信息	查看全文 | 推荐本文 |

• 作者：Margaret  ; A. Young¹ ; David  ; E. Larson² ; Chiao-Wang Sun⁶ ; Daniel  ; R. George¹ ; Li Ding² ; ³ ; Christopher  ; A. Miller² ; Ling Lin² ; Kevin  ; M. Pawlik⁶ ; Ken Chen⁷ ; Xian Fan² ; Heather Schmidt² ; Joelle Kalicki-Veizer² ; Lisa  ; L. Cook² ; Gary  ; W. Swift² ; Ryan  ; T. Demeter² ; Michael  ; C. Wendl² ; ³ ; ⁴ ; Mark  ; S. Sands¹ ; Elaine  ; R. Mardis² ; ³ ; ⁵ ; Richard  ; K. Wilson² ; ³ ; ⁵ ; Tim  ; M. Townes⁶ ; Timothy  ; J. Ley¹ ; ² ; ³ ; ⁵ ; ^{timley@wustl.edu}
• 刊名：Cell Stem Cell
• 出版年：2012
• 期刊代码：P15_19345909
• 类别：bio
• 出版时间：4 May, 2012
• 卷：10
• 期：5
• 页码：570-582
• 文件大小：1379 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferencesml version="1.0" encoding="UTF-8"?>

Summary

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 鈥渃aptures鈥?their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.