Embryonic Stem Cells/induced Pluripotent Stem Cells

Regulation of L-Threonine Dehydrogenase in Somatic Cell Reprogramming†‡§

  1. Chuanchun Han,
  2. Hao Gu,
  3. Jiaxu Wang,
  4. Weiguang Lu,
  5. Yide Mei¶,*,
  6. Mian Wu‖,*

Article first published online: 24 APR 2013

DOI: 10.1002/stem.1335

Issue

STEM CELLS

STEM CELLS

Volume 31, Issue 5, pages 953–965, May 2013

Additional Information

How to Cite

Han, C., Gu, H., Wang, J., Lu, W., Mei, Y. and Wu, M. (2013), Regulation of L-Threonine Dehydrogenase in Somatic Cell Reprogramming. STEM CELLS, 31: 953–965. doi: 10.1002/stem.1335

Author Information

  1. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China

  1. Telephone: 86-551-3600921; Fax: 86-551-3600921;

  2. ‖

    Telephone: 86-551-3606264; Fax: 86-551-3606264

*Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China

  1. †

    Author contributions: C.H.: conceived the project and analyzed the data; performed all the experiments with the help of J.W. and W.L.; H.G.: performed all the experiments with the help of J.W. and W.L.; Y.M. and M.W.: conceived the project and analyzed the data; wrote the manuscript with the help of C.H. All the authors discussed the results and commented on the manuscript. C.H. and H.G. contributed equally to this work.

  2. ‡

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

  3. §

    First published online in STEM CELLSEXPRESS January 25, 2013.

  4. Telephone: 86-551-3600921; Fax: 86-551-3600921;

  5. ‖

    Telephone: 86-551-3606264; Fax: 86-551-3606264

Publication History

  1. Issue published online: 24 APR 2013
  2. Article first published online: 24 APR 2013
  3. Accepted manuscript online: 25 JAN 2013 07:19AM EST
  4. Manuscript Accepted: 21 DEC 2012
  5. Manuscript Received: 27 SEP 2012

Funded by

  • Chinese Academy of Sciences. Grant Number: XDA01020104
  • Ministry of Science and Technology of China. Grant Numbers: 2010CB912804, 2011CB966302
  • National Natural Science Foundation of China. Grant Number: 31030046
  • Fundamental Research Funds for Central Universities. Grant Number: WK2060190018

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Keywords:

  • TDH;
  • miR-9;
  • PRMT5;
  • Arginine methylation;
  • Somatic cell reprogramming

Abstract

Increasing evidence suggests that metabolic remodeling plays an important role in the regulation of somatic cell reprogramming. Threonine catabolism mediated by L-threonine dehydrogenase (TDH) has been recognized as a specific metabolic trait of mouse embryonic stem cells. However, it remains unknown whether TDH-mediated threonine catabolism could regulate reprogramming. Here, we report TDH as a novel regulator of somatic cell reprogramming. Knockdown of TDH inhibits, whereas induction of TDH enhances reprogramming efficiency. Moreover, microRNA-9 post-transcriptionally regulates the expression of TDH and thereby inhibits reprogramming efficiency. Furthermore, protein arginine methyltransferase (PRMT5) interacts with TDH and mediates its post-translational arginine methylation. PRMT5 appears to regulate TDH enzyme activity through both methyltransferase-dependent and -independent mechanisms. Functionally, TDH-facilitated reprogramming efficiency is further enhanced by PRMT5. These results suggest that TDH-mediated threonine catabolism controls somatic cell reprogramming and indicate the importance of post-transcriptional and post-translational regulation of TDH. STEM CELLS 2013;31:953–965

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