Epigenetic memory in induced pluripotent stem cells

被引：1631

作者：

Kim, K. ^{[3
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,5
,6
,7
]}

Doi, A. ^{[1
,2
]}

Wen, B. ^{[1
,2
]}

Ng, K. ^{[3
,4
,5
,6
,7
]}

Zhao, R. ^{[3
,4
,5
,6
,7
]}

Cahan, P. ^{[3
,4
,5
,6
,7
]}

Kim, J. ^{[4
,8
]}

Aryee, M. J. ^{[9
]}

Ji, H. ^{[1
,2
]}

Ehrlich, L. I. R. ^{[10
]}

Yabuuchi, A. ^{[3
,4
,5
,6
,7
]}

Takeuchi, A. ^{[3
,4
,5
,6
,7
]}

Cunniff, K. C. ^{[3
,4
,5
,6
,7
]}

Hongguang, H. ^{[3
,4
,5
,6
,7
]}

Mckinney-Freeman, S. ^{[3
,4
,5
,6
,7
]}

Naveiras, O. ^{[3
,4
,5
,6
,7
]}

Yoon, T. J. ^{[11
]}

Irizarry, R. A. ^{[1
,2
]}

Jung, N. ^{[1
,2
]}

Seita, J. ^{[10
]}

Hanna, J. ^{[12
]}

Murakami, P. ^{[1
,2
]}

Jaenisch, R. ^{[12
]}

Weissleder, R. ^{[11
]}

Orkin, S. H. ^{[4
,8
]}

Weissman, I. L. ^{[10
]}

Feinberg, A. P. ^{[1
,2
]}

Daley, G. Q. ^{[3
,4
,5
,6
,7
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[7] Harvard Stem Cell Inst, Boston, MA 02115 USA

[8] Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[9] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA

[10] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[11] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA

[12] MIT, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

来源：

NATURE | 2010年 / 467卷 / 7313期

关键词：

MAMMALIAN-CELLS; DNA METHYLATION; IPS CELLS; DIFFERENTIATION; TISSUE; GENERATION; MICE; ACTIVATION; MICROARRAY; SYSTEM;

D O I：

10.1038/nature09342

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer more readily establishes the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.

引用

页码：285 / U60

页数：8

共 54 条

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