Downregulation of STAT1 induces the differentiation of neural stem cells through JNK pathway

Tissue Cell. 2019 Dec:61:61-66. doi: 10.1016/j.tice.2019.09.004. Epub 2019 Sep 16.

Abstract

Neural stem cells (NSCs) generated neurons and glial cells. Thus, it is a preferable candidate to the cell replacement-based therapy against neural disorders. The signaling pathways that regulate differentiation of NSCs are widely studied. In the current study, we used in vitro culture system to elucidate the role of signal transducer and activator of transcription 1 (STAT1) in NSCs' differentiation. Downregulation of STAT1 inhibited the proliferation of NSCs. Meanwhile, we also found STAT1 regulation could control the differentiation of NSCs. More neurons and glia cells were generated from NSCs with STAT1 silencing. This process was mediated by the JNK/STAT1 signaling. STAT1 inhibitor promoted differentiation of NSCs. After transplantation, we observed more neurons generated from NSCs with shRNA-STAT1 treatment. Collectively, this work showed an efficient way to regulate neuronal differentiation of NSCs through regulating the STAT1 expression. This is likely to provide source and theoretical support to cell replacement based theory.

Keywords: Differentiation; Neural stem cells; Neurons; STAT1.

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • Down-Regulation / genetics*
  • Gene Silencing
  • MAP Kinase Signaling System*
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / transplantation
  • Neurons / cytology
  • RNA, Small Interfering / metabolism
  • STAT1 Transcription Factor / metabolism*

Substances

  • RNA, Small Interfering
  • STAT1 Transcription Factor