Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1 = Bmi1을 통한 만능유도줄기세포로의 리프로그래밍

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Title
Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1 = Bmi1을 통한 만능유도줄기세포로의 리프로그래밍
Author(s)
J H Moon; J S Heo; J S Kim; E K Jun; J H Lee; A Kim; J Kim; K Y Whang; Yong-Kook Kang; S Yeo; H J Lim; D W Han; D W Kim; S Oh; B S Yoon; H R Scholer; S You
Bibliographic Citation
Cell Research, vol. 21, no. 9, pp. 1305-1315
Publication Year
2011
Abstract
Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 leads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedgehog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differentiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data support that converting fibroblasts with Bmi1 or activation of the sonic hedgehog pathway to an intermediate cell type that expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4.
Keyword
Bmi1induced pluripotent stem cellsneural stem cellsOct4reprogrammingtransdifferentiation
ISSN
1001-0602
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/cr.2011.107
Type
Article
Appears in Collections:
Division of Research on National Challenges > Aging Research Center > 1. Journal Articles
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