Low Incidence of DNA Sequence Variation in Human Induced Pluripotent Stem Cells Generated by Nonintegrating Plasmid Expression

被引：207

作者：

Cheng, Linzhao ^{[1
,2
]}

Hansen, Nancy F. ^{[3
]}

Zhao, Ling ^{[4
]}

Du, Yutao ^{[6
]}

Zou, Chunlin ^{[1
,2
]}

Donovan, Frank X.

Chou, Bin-Kuan ^{[1
,2
]}

Zhou, Guangyu ^{[6
]}

Li, Shijie ^{[6
]}

Dowey, Sarah N. ^{[1
,2
]}

Ye, Zhaohui ^{[1
,2
]}

Chandrasekharappa, Settara C.

Yang, Huanming ^{[6
]}

Mullikin, James C. ^{[3
,5
]}

Liu, P. Paul ^{[4
]}

机构：

[1] Johns Hopkins Univ, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Div Hematol, Baltimore, MD 21205 USA

[3] NHGRI, Comparat Genom Unit, NIH, Bethesda, MD 20892 USA

[4] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA

[5] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA

[6] Beijing Genom Inst BGI Shenzhen, Shenzhen 518000, Peoples R China

来源：

CELL STEM CELL | 2012年 / 10卷 / 03期

关键词：

COPY NUMBER VARIATION; MUTATIONS; ACCURATE; DERIVATION; SPECTRUM;

D O I：

10.1016/j.stem.2012.01.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The utility of induced pluripotent stem cells (iPSCs) as models to study diseases and as sources for cell therapy depends on the integrity of their genomes. Despite recent publications of DNA sequence variations in the iPSCs, the true scope of such changes for the entire genome is not clear. Here we report the whole-genome sequencing of three human iPSC lines derived from two cell types of an adult donor by episomal vectors. The vector sequence was undetectable in the deeply sequenced iPSC lines. We identified 1,058-1,808 heterozygous single-nucleotide variants (SNVs), but no copy-number variants, in each iPSC line. Six to twelve of these SNVs were within coding regions in each iPSC line, but 50% of them are synonymous changes and the remaining are not selectively enriched for known genes associated with cancers. Our data thus suggest that episome-mediated reprogramming is not inherently mutagenic during integration-free iPSC induction.

引用

页码：337 / 344

页数：8

共 25 条

[21] Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells [J].

Polo, Jose M. ;

Liu, Susanna ;

Figueroa, Maria Eugenia ;

Kulalert, Warakorn ;

Eminli, Sarah ;

Tan, Kah Yong ;

Apostolou, Effie ;

Stadtfeld, Matthias ;

Li, Yushan ;

Shioda, Toshi ;

Natesan, Sridaran ;

Wagers, Amy J. ;

Melnick, Ari ;

Evans, Todd ;

Hochedlinger, Konrad .

NATURE BIOTECHNOLOGY, 2010, 28 (08) :848-U130

[22] PennCNV: An integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data [J].

Wang, Kai ;

Li, Mingyao ;

Hadley, Dexter ;

Liu, Rui ;

Glessner, Joseph ;

Grant, Struan F. A. ;

Hakonarson, Hakon ;

Bucan, Maja .

GENOME RESEARCH, 2007, 17 (11) :1665-1674

[23] CNV-seq, a new method to detect copy number variation using high-throughput sequencing [J].

Xie, Chao ;

Tammi, Martti T. .

BMC BIOINFORMATICS, 2009, 10

[24] Sensitive and accurate detection of copy number variants using read depth of coverage [J].

Yoon, Seungtai ;

Xuan, Zhenyu ;

Makarov, Vladimir ;

Ye, Kenny ;

Sebat, Jonathan .

GENOME RESEARCH, 2009, 19 (09) :1586-1592

[25] Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences [J].

Yu, Junying ;

Hu, Kejin ;

Smuga-Otto, Kim ;

Tian, Shulan ;

Stewart, Ron ;

Slukvin, Igor I. ;

Thomson, James A. .

SCIENCE, 2009, 324 (5928) :797-801

← 1 2 3 →