Critical Role of Tet3 in Neural Progenitor Cell Maintenance and Terminal Differentiation

Ting Li, Dehua Yang, Jia Li, Yu Tang, Juan Yang, Weidong Le

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytocine (5mC) by Tet family of dioxygenases (Tet1, Tet2, and Tet3), is enriched in the embryonic stem cells (ESCs) and in the brain. However, the role of 5hmC and Tet family in the process of ESC differentiation especially neuronal differentiation remains elusive. Here, we showed the evidence that Tet3 is critical in neural progenitor cell (NPC) maintenance and terminal differentiation of neurons. We found that Tet3 expression is basically undetectable in ESCs, but its level increases rapidly during neuronal differentiation. Tet3 knockout ESCs appear normal in self-renewal and maintenance but impaired in neuronal differentiation. NPCs could be induced efficiently from Tet3 knockout ESCs, as the expression of NPC marker Pax6 and nestin is comparable with NPCs from wild-type ESCs, but undergo apoptosis rapidly, and the terminal differentiation of neurons is greatly reduced. Our results indicate that Tet3 is important for NPC maintenance and terminal differentiation of neurons.

Original languageEnglish (US)
Pages (from-to)142-154
Number of pages13
JournalMolecular Neurobiology
Volume51
Issue number1
DOIs
StatePublished - Feb 2014

Keywords

  • 5hmC
  • Embryonic stem cells
  • Neural differentiation
  • Neural progenitor cells
  • Tet family

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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