Volume 21, No 9, Sep 2011
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 21 Issue 9, September 2011: 1305-1315
ORIGINAL ARTICLES
Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1
Jai-Hee Moon1, June Seok Heo1, Jun Sung Kim1, Eun Kyoung Jun1,2, Jung Han Lee1,2, Aeree Kim3, Jonggun Kim4, Kwang Youn Whang4, Yong-Kook Kang5, Seungeu
1Laboratory of Cell Function Regulation, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea
2Division of Stem Cell Research Institute, Stemmedience Corp., Seoul, Republic of Korea
3Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
4Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
5Development and Differentiation Research Center, KRIBB, Daejeon 305-333, Republic of Korea
6Department of Stem Cell Biology, SMART Institute of Advanced Biomedical Science, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea
7Department of Physiology, Center for Cell Therapy, Yonsei University College of Medicine, Seoul, Republic of Korea
8Division of Animal Science, Chonnam National University, Gwangju 500-757, Republic of Korea
9Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, R鰊tgenstra遝 20, M黱ster D-48149, Germany
10Medical Faculty, University of M黱ster, Domagkstr. 3, M黱ster D-48149, Germany
Correspondence: Seungkwon You, Hans R Sch鰈er, Byung Sun Yoon,(bioseung@korea.ac.kr; office@mpi-muenster.mpg.de;biosun302@korea.ac.kr)
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.
Cell Research (2011) 21:1305-1315. doi:10.1038/cr.2011.107; published online 28 June 2011
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