Embryonic Stem Cells/Induced Pluripotent Stem Cells

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Brief Report: Combined Chemical Treatment Enables Oct4-Induced Reprogramming from Mouse Embryonic Fibroblasts†‡§

  1. Xu Yuan1,
  2. Haifeng Wan2,3,
  3. Xiaoyang Zhao2,3,
  4. Saiyong Zhu1,
  5. Qi Zhou2,
  6. Sheng Ding1,¶,*

Article first published online: 21 MAR 2011

DOI: 10.1002/stem.594

Issue

STEM CELLS

STEM CELLS

Volume 29, Issue 3, pages 549–553, March 2011

Additional Information

How to Cite

Yuan, X., Wan, H., Zhao, X., Zhu, S., Zhou, Q. and Ding, S. (2011), Brief Report: Combined Chemical Treatment Enables Oct4-Induced Reprogramming from Mouse Embryonic Fibroblasts. STEM CELLS, 29: 549–553. doi: 10.1002/stem.594

Author Information

  1. 1

    Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA

  2. 2

    State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China

  3. 3

    Graduate School of Chinese Academy of Sciences, Beijing, People's Republic of China

  1. Telephone: 1-858-784-7376; Fax: 1-858-784-7882

*Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA

  1. †

    Disclosure of potential conflicts of interest is found at the end of this article.

  2. ‡

    Author contributions: X.Y.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; H.W.: collection and/or assembly of data, data analysis and interpretation; X.Z.: collection and/or assembly of data; S.Z.: collection and/or assembly of data; Q.Z.: conception and design, financial support; S.D.: conception and design, financial support, manuscript writing, final approval of manuscript. X.Y. and H.W. contributed equally to this work.

  3. §

    First published online in STEM CELLSEXPRESS January 7, 2011.

  4. Telephone: 1-858-784-7376; Fax: 1-858-784-7882

Publication History

  1. Issue published online: 21 MAR 2011
  2. Article first published online: 21 MAR 2011
  3. Accepted manuscript online: 7 JAN 2011 03:31PM EST
  4. Manuscript Accepted: 18 DEC 2010
  5. Manuscript Received: 22 NOV 2010

Funded by

  • NICHD
  • NHLBI
  • NIMH/NIH
  • California Institute for Regenerative Medicine
  • Prostate Cancer Foundation
  • Fate Therapeutics
  • Esther B. O'Keeffe Foundation
  • The Scripps Research Institute
  • National Science Foundation of China. Grant Number: 90919060
  • China National Basic Research Program. Grant Number: 2011CB965301

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Keywords:

  • Reprogramming;
  • iPSC;
  • TGF-β;
  • Pluripotent stem cells

Abstract

It has been established that exogenous expression of four transcription factors (Oct4, Klf4, Sox2, and c-Myc) can reprogram mammalian somatic cells to pluripotent states. Further studies demonstrated that such induced pluripotent stem cells (iPSCs) could be generated with fewer exogenous transcription factors, facilitated by endogenous expression of reprogramming factors and/or synthetic small molecules. Here, we reported identification of a new small molecule, a protein arginine methyltransferase inhibitor AMI-5, which enabled Oct4-induced reprogramming of mouse embryonic fibroblasts in combination with transforming growth factor (TGF)-β inhibitor A-83-01. The Oct4-induced iPSCs were shown similar to mouse embryonic stem cells with respect to typical pluripotency criteria. More importantly, they were shown to give rise to liveborn pups through tetraploid complementation assays, demonstrating the high quality of full reprogramming induced by this condition. Furthermore, this study suggests that regulation of protein arginine methylation might be involved in the reprogramming process. STEM CELLS 2011;29:549–553

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