Cell Reports (Dec 2023)

BACH1 regulates the differentiation of vascular smooth muscle cells from human embryonic stem cells via CARM1-mediated methylation of H3R17

  • Yunquan He,
  • Jieyu Guo,
  • Yueyang Yu,
  • Jiayu Jin,
  • Qingjun Jiang,
  • Qinhan Li,
  • Siyu Ma,
  • Qi Pan,
  • Jiayi Lin,
  • Nan Jiang,
  • Jinghua Ma,
  • Yongbo Li,
  • Yannan Hou,
  • Xiuling Zhi,
  • Lindi Jiang,
  • Lefeng Qu,
  • Elena Osto,
  • Xinhong Wang,
  • Xiangxiang Wei,
  • Dan Meng

Journal volume & issue
Vol. 42, no. 12
p. 113468

Abstract

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Summary: The role of BACH1 in the process of vascular smooth muscle cell (VSMC) differentiation from human embryonic stem cells (hESCs) remains unknown. Here, we find that the loss of BACH1 in hESCs attenuates the expression of VSMC marker genes, whereas overexpression of BACH1 after mesoderm induction increases the expression of VSMC markers during in vitro hESC-VSMC differentiation. Mechanistically, BACH1 binds directly to coactivator-associated arginine methyltransferase 1 (CARM1) during in vitro hESC-VSMC differentiation, and this interaction is mediated by the BACH1 bZIP domain. BACH1 recruits CARM1 to VSMC marker gene promoters and promotes VSMC marker expression by increasing H3R17me2 modification, thus facilitating in vitro VSMC differentiation from hESCs after the mesoderm induction. The increased expression of VSMC marker genes by BACH1 overexpression is partially abolished by inhibition of CARM1 or the H3R17me2 inhibitor TBBD in hESC-derived cells. These findings highlight the critical role of BACH1 in hESC differentiation into VSMCs by CARM1-mediated methylation of H3R17.

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