Intrinsic transition of embryonic stem-cell differentiation into neural progenitors

Daisuke Kamiya, Satoe Banno, Noriaki Sasai, Masatoshi Ohgushi, Hidehiko Inomata, Kiichi Watanabe, Masako Kawada, Rieko Yakura, Hiroshi Kiyonari, Kazuki Nakao, Lars Martin Jakt, Shin Ichi Nishikawa, Yoshiki Sasai

Research output: Contribution to journalArticlepeer-review

165 Citations (Scopus)

Abstract

The neural fate is generally considered to be the intrinsic direction of embryonic stem (ES) cell differentiation. However, little is known about the intracellular mechanism that leads undifferentiated cells to adopt the neural fate in the absence of extrinsic inductive signals. Here we show that the zinc-finger nuclear protein Zfp521 is essential and sufficient for driving the intrinsic neural differentiation of mouse ES cells. In the absence of the neural differentiation inhibitor BMP4, strong Zfp521 expression is intrinsically induced in differentiating ES cells. Forced expression of Zfp521 enables the neural conversion of ES cells even in the presence of BMP4. Conversely, in differentiation culture, Zfp521-depleted ES cells do not undergo neural conversion but tend to halt at the epiblast state. Zfp521 directly activates early neural genes by working with the co-activator p300. Thus, the transition of ES cell differentiation from the epiblast state into neuroectodermal progenitors specifically depends on the cell-intrinsic expression and activator function of Zfp521.

Original languageEnglish
Pages (from-to)503-510
Number of pages8
JournalNature
Volume470
Issue number7335
DOIs
Publication statusPublished - 24-02-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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