Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells

被引：344

作者：

Eminli, Sarah ^{[1
,2
,3
,4
,5
]}

Foudi, Adlen ^{[1
,2
,4
]}

Stadtfeld, Matthias ^{[1
,2
,3
,4
]}

Maherali, Nimet ^{[1
,2
,3
,4
,6
]}

Ahfeldt, Tim ^{[1
,2
,7
]}

Mostoslavsky, Gustavo ^{[8
,9
]}

Hock, Hanno ^{[1
,2
,4
]}

Hochedlinger, Konrad ^{[1
,2
,3
,4
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA

[2] Ctr Regenerat Med, Boston, MA USA

[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[4] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA

[5] Free Univ Berlin, Dept Biol Chem & Pharm, D-1000 Berlin, Germany

[6] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[7] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol 2, Hamburg, Germany

[8] Boston Univ, Sch Med, Gastroenterol Sect, Dept Med, Boston, MA 02118 USA

[9] Boston Univ, Ctr Regenerat Med, Boston, MA 02215 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 09期

关键词：

HUMAN SOMATIC-CELLS; HUMAN FIBROBLASTS; PROGENITOR CELLS; NUCLEAR TRANSFER; MATURE B; GENERATION; INDUCTION; SYSTEM; OCT4; EXPRESSION;

D O I：

10.1038/ng.428

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is inefficient. It has been assumed that the somatic differentiation state provides a barrier for efficient reprogramming; however, direct evidence for this notion is lacking. Here, we tested the potential of mouse hematopoietic cells at different stages of differentiation to be reprogrammed into iPS cells. We show that hematopoietic stem and progenitor cells give rise to iPS cells up to 300 times more efficiently than terminally differentiated B and T cells do, yielding reprogramming efficiencies of up to 28%. Our data provide evidence that the differentiation stage of the starting cell has a critical influence on the efficiency of reprogramming into iPS cells. Moreover, we identify hematopoietic progenitors as an attractive cell type for applications of iPS cell technology in research and therapy.

引用

页码：968 / U29

页数：11

共 51 条

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