Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1

Jai Hee Moon, June Seok Heo, Jun Sung Kim, Eun Kyoung Jun, Jung Han Lee, Aeree Kim, Jonggun Kim, Kwang Youn Whang, Yong Kook Kang, Seungeun Yeo, Hee Joung Lim, Dong Wook Han, Dong Wook Kim, Sejong Oh, Byung Sun Yoon, Hans R. Schöler, Seungkwon You

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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.

Original languageEnglish
Pages (from-to)1305-1315
Number of pages11
JournalCell Research
Volume21
Issue number9
DOIs
Publication statusPublished - 2011 Sep 1

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Keywords

  • Bmi1
  • induced pluripotent stem cells
  • neural stem cells
  • Oct4
  • reprogramming
  • transdifferentiation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Moon, J. H., Heo, J. S., Kim, J. S., Jun, E. K., Lee, J. H., Kim, A., Kim, J., Whang, K. Y., Kang, Y. K., Yeo, S., Lim, H. J., Han, D. W., Kim, D. W., Oh, S., Yoon, B. S., Schöler, H. R., & You, S. (2011). Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1. Cell Research, 21(9), 1305-1315. https://doi.org/10.1038/cr.2011.107