LncRNA SOX1-OT V1 acts as a decoy of HDAC10 to promote SOX1-dependent hESC neuronal differentiation

EMBO Rep. 2022 Feb 3;23(2):e53015. doi: 10.15252/embr.202153015. Epub 2021 Dec 20.

Abstract

Long noncoding RNAs (lncRNAs) are abundantly expressed in the nervous system, but their regulatory roles in neuronal differentiation are poorly understood. Using a human embryonic stem cell (hESC)-based 2D neural differentiation approach and a 3D cerebral organoid system, we show that SOX1-OT variant 1 (SOX1-OT V1), a SOX1 overlapping noncoding RNA, plays essential roles in both dorsal cortical neuron differentiation and ventral GABAergic neuron differentiation by facilitating SOX1 expression. SOX1-OT V1 physically interacts with HDAC10 through its 5' region, acts as a decoy to block HDAC10 binding to the SOX1 promoter, and thus maintains histone acetylation levels at the SOX1 promoter. SOX1 in turn activates ASCL1 expression and promotes neuronal differentiation. Taken together, we identify a SOX1-OT V1/HDAC10-SOX1-ASCL1 axis, which promotes neurogenesis, highlighting a role for lncRNAs in hESC neuronal differentiation.

Keywords: SOX1-OT; HDAC10; human embryonic stem cell; long noncoding RNAs; neuronal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Histone Deacetylases / metabolism
  • Human Embryonic Stem Cells* / cytology
  • Humans
  • Neurons / cytology*
  • Neurons / metabolism
  • RNA, Long Noncoding* / genetics
  • SOXB1 Transcription Factors* / genetics
  • SOXB1 Transcription Factors* / metabolism

Substances

  • RNA, Long Noncoding
  • SOX1 protein, human
  • SOXB1 Transcription Factors
  • HDAC10 protein, human
  • Histone Deacetylases