Frontiers in Cell and Developmental Biology (Oct 2021)

Tet1 Regulates Astrocyte Development and Cognition of Mice Through Modulating GluA1

  • Weize Xu,
  • Weize Xu,
  • Xicheng Zhang,
  • Xicheng Zhang,
  • Feng Liang,
  • Yuhang Cao,
  • Yuhang Cao,
  • Yuhang Cao,
  • Ziyi Li,
  • Wenzheng Qu,
  • Wenzheng Qu,
  • Jinyu Zhang,
  • Jinyu Zhang,
  • Jinyu Zhang,
  • Yanhua Bi,
  • Chongran Sun,
  • Jianmin Zhang,
  • Binggui Sun,
  • Qiang Shu,
  • Qiang Shu,
  • Xuekun Li,
  • Xuekun Li,
  • Xuekun Li

DOI
https://doi.org/10.3389/fcell.2021.644375
Journal volume & issue
Vol. 9

Abstract

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Tet (Ten eleven translocation) family proteins-mediated 5-hydroxymethylcytosine (5hmC) is highly enriched in the neuronal system, and is involved in diverse biological processes and diseases. However, the function of 5hmC in astrocyte remains completely unknown. In the present study, we show that Tet1 deficiency alters astrocyte morphology and impairs neuronal function. Specific deletion of Tet1 in astrocyte impairs learning and memory ability of mice. Using 5hmC high-throughput DNA sequencing and RNA sequencing, we present the distribution of 5hmC among genomic features in astrocyte and show that Tet1 deficiency induces differentially hydroxymethylated regions (DhMRs) and alters gene expression. Mechanistically, we found that Tet1 deficiency leads to the abnormal Ca2+ signaling by regulating the expression of GluA1, which can be rescued by ectopic GluA1. Collectively, our findings suggest that Tet1 plays important function in astrocyte physiology by regulating Ca2+ signaling.

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