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Intrinsic transition of embryonic stem-cell differentiation into neural progenitors

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  • Daisuke Kamiya

    (Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan
    Kyoto University Graduate School of Medicine, Kyoto 606-8501, 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
    Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan)

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.

Suggested Citation

  • 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 Ni, 2011. "Intrinsic transition of embryonic stem-cell differentiation into neural progenitors," Nature, Nature, vol. 470(7335), pages 503-509, February.
  • Handle: RePEc:nat:nature:v:470:y:2011:i:7335:d:10.1038_nature09726
    DOI: 10.1038/nature09726
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    Cited by:

    1. Anat Kreimer & Tal Ashuach & Fumitaka Inoue & Alex Khodaverdian & Chengyu Deng & Nir Yosef & Nadav Ahituv, 2022. "Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Balazs V. Varga & Maryam Faiz & Helena Pivonkova & Gabriel Khelifi & Huijuan Yang & Shangbang Gao & Emma Linderoth & Mei Zhen & Ragnhildur Thora Karadottir & Samer M. Hussein & Andras Nagy, 2022. "Signal requirement for cortical potential of transplantable human neuroepithelial stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Luca Salerno & Carlo Cosentino & Giovanni Morrone & Francesco Amato, 2015. "Computational Modeling of a Transcriptional Switch Underlying B-Lymphocyte Lineage Commitment of Hematopoietic Multipotent Cells," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-23, July.

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