Suppression of oct4 by germ cell nuclear factor restricts pluripotency and promotes neural stem cell development in the early neural lineage

Wado Akamatsu, Brian Deveale, Hideyuki Okano, Austin J. Cooney, Derek Der Van Kooy

研究成果: Article

57 引用 (Scopus)

抄録

The earliest murine neural stem cells are leukemia inhibitory factor (LIF)-dependent, primitive neural stem cells, which can be isolated from embryonic stem cells or early embryos. These primitive neural stem cells have the ability to differentiate to non-neural tissues and transition into FGF2-dependent, definitive neural stem cells between embryonic day 7.5 and 8.5 in vivo, accompanied by a decrease in non-neural competency. We found that Oct4 is expressed in LIF-dependent primitive neural stem cells and suppressed in FGF-dependent definitive neural stem cells. In mice lacking germ cell nuclear factor (GCNF), a transcriptional repressor of Oct4, generation of definitive neural stem cells was dramatically suppressed, accompanied by a sustained expression of Oct4 in the early neuroectoderm. Knockdown of Oct4 in GCNF neural stem cells rescued the GCNF phenotype. Overexpession of Oct4 blocked the differentiation of primitive to definitive neural stem cells, but did not induce the dedifferentiation of definitive to primitive neural stem cells. These results suggested that primitive neural stem cells develop into definitive neural stem cells by means of GCNF induced suppression of Oct4. The Oct4 promoter was methylated during the development from primitive neural stem cell to definitive neural stem cell, while these neural stem cells lose their pluripotency through a GCNF dependent mechanism. Thus, the suppression of Oct4 by GCNF is important for the transition from primitive to definitive neural stem cells and restriction of the non-neural competency in the early neural stem cell lineage.

元の言語English
ページ(範囲)2113-2124
ページ数12
ジャーナルJournal of Neuroscience
29
発行部数7
DOI
出版物ステータスPublished - 2009 2 18

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Nuclear Receptor Subfamily 6, Group A, Member 1
Neural Stem Cells
Leukemia Inhibitory Factor

ASJC Scopus subject areas

  • Neuroscience(all)

これを引用

Suppression of oct4 by germ cell nuclear factor restricts pluripotency and promotes neural stem cell development in the early neural lineage. / Akamatsu, Wado; Deveale, Brian; Okano, Hideyuki; Cooney, Austin J.; Van Kooy, Derek Der.

:: Journal of Neuroscience, 巻 29, 番号 7, 18.02.2009, p. 2113-2124.

研究成果: Article

Akamatsu, Wado ; Deveale, Brian ; Okano, Hideyuki ; Cooney, Austin J. ; Van Kooy, Derek Der. / Suppression of oct4 by germ cell nuclear factor restricts pluripotency and promotes neural stem cell development in the early neural lineage. :: Journal of Neuroscience. 2009 ; 巻 29, 番号 7. pp. 2113-2124.
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