The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells

  1. Taeko Kobayashi1,2,8,
  2. Hiroaki Mizuno1,2,3,
  3. Itaru Imayoshi1,2,3,
  4. Chikara Furusawa4,5,
  5. Katsuhiko Shirahige6 and
  6. Ryoichiro Kageyama1,2,7
  1. 1Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan;
  2. 2Japan Science and Technology Agency, CREST, Kyoto 606-8507, Japan;
  3. 3Kyoto University Graduate School of Biostudies, Kyoto 606-8502, Japan;
  4. 4Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita 565-0871, Japan;
  5. 5Japan Science and Technology Agency, ERATO, Suita 565-0871, Japan;
  6. 6Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan

    Abstract

    Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. Thus, Hes1-null ES cells display less heterogeneity in both the differentiation timing and fate choice, suggesting that the cyclic gene Hes1 contributes to heterogeneous responses of ES cells even under the same environmental conditions.

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    1. doi: 10.1101/gad.1823109 Genes & Dev. 23: 1870-1875 Copyright © 2009 by Cold Spring Harbor Laboratory Press

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