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 and Yoshiki Sasai ()
Additional contact information
Daisuke Kamiya: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Satoe Banno: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Noriaki Sasai: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Masatoshi Ohgushi: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Hidehiko Inomata: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Kiichi Watanabe: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Masako Kawada: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Rieko Yakura: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Hiroshi Kiyonari: Laboratory of Animal Resource and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Kazuki Nakao: Laboratory of Animal Resource and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Lars Martin Jakt: Laboratory of Stem Cell Research, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Shin-ichi Nishikawa: Laboratory of Stem Cell Research, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
Yoshiki Sasai: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan

Nature, 2011, vol. 470, issue 7335, 503-509

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature09726

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