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

doi:10.1038/nature09726

Intrinsic transition of embryonic stem-cell differentiation into neural progenitors

Nature. 2011 Feb 24;470(7335):503-9. doi: 10.1038/nature09726. Epub 2011 Feb 16.

Authors

Daisuke Kamiya¹, 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

Affiliation

¹ Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.

PMID: 21326203
DOI: 10.1038/nature09726

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Morphogenetic Protein 4 / deficiency
Bone Morphogenetic Protein 4 / genetics
Bone Morphogenetic Protein 4 / metabolism
Cadherins / metabolism
Cell Differentiation*
Cell Lineage
Cells, Cultured
Embryo, Mammalian / cytology
Embryo, Mammalian / embryology
Embryo, Mammalian / metabolism
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / metabolism
Gene Expression Regulation, Developmental / genetics
Germ Layers / cytology
Germ Layers / embryology
Germ Layers / metabolism
HEK293 Cells
Humans
Mice
Models, Biological
Neural Plate / cytology
Neural Plate / embryology
Neural Plate / metabolism
Neural Stem Cells / cytology*
Neural Stem Cells / metabolism
Oligonucleotide Array Sequence Analysis
SOXB1 Transcription Factors / metabolism
Transcription Factors / deficiency
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptional Activation
Xenopus
p300-CBP Transcription Factors / metabolism

Substances

Bmp4 protein, mouse
Bone Morphogenetic Protein 4
Cadherins
Evi3 protein, mouse
SOXB1 Transcription Factors
Sox1 protein, mouse
Transcription Factors
p300-CBP Transcription Factors

Associated data

GEO/GSE25593