The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection

被引：144

作者：

Buganim, Yosef ^{[2
]}

Markoulaki, Styliani ^{[1
]}

van Wietmarschen, Niek ^{[3
]}

Hoke, Heather ^{[1
,4
]}

Wu, Tao ^{[5
]}

Ganz, Kibibi ^{[1
]}

Akhtar-Zaidi, Batool ^{[1
]}

He, Yupeng ^{[6
]}

Abraham, Brian J. ^{[1
]}

Porubsky, David ^{[3
]}

Kulenkampff, Elisabeth ^{[1
]}

Faddah, Dina A. ^{[1
,4
]}

Shi, Linyu ^{[1
]}

Gao, Qing ^{[1
]}

Sarkar, Sovan ^{[1
]}

Cohen, Malkiel ^{[1
]}

Goldmann, Johanna ^{[1
]}

Nery, Joseph R. ^{[6
]}

Schultz, Matthew D. ^{[6
]}

Ecker, Joseph R. ^{[6
]}

Xiao, Andrew ^{[5
]}

Young, Richard A. ^{[1
,4
,7
]}

Lansdorp, Peter M. ^{[3
,7
]}

Jaenisch, Rudolf ^{[1
,4
,7
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel

[3] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, NL-9713 AV Groningen, Netherlands

[4] MIT, Dept Biol, Cambridge, MA 02139 USA

[5] Yale Univ, Yale Stem Cell Ctr, New Haven, CT 06520 USA

[6] Salk Inst Biol Studies, Howard Hughes Med Inst, Genom Anal Lab, La Jolla, CA 92037 USA

[7] Skolkovo Inst Sci & Technol Skoltech, Skolkovo 143025, Moscow Region, Russia

来源：

CELL STEM CELL | 2014年 / 15卷 / 03期

基金：

美国国家科学基金会;

关键词：

PLURIPOTENT STEM-CELLS; ES CELLS; TETRAPLOID COMPLEMENTATION; C-MYC; EPIGENETIC MEMORY; SUPER-ENHANCERS; TRANSGENIC MICE; SINGLE-CELLS; COPY NUMBER; DNA-DAMAGE;

D O I：

10.1016/j.stem.2014.07.003

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A. X deposition were distinguishing features that could potentially also be applicable to human.

引用

页码：295 / 309

页数：15

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