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

被引：3

作者：

He, Yunquan ^{[1
]}

Guo, Jieyu ^{[1
]}

Yu, Yueyang ^{[1
]}

Jin, Jiayu ^{[1
]}

Jiang, Qingjun ^{[1
,2
]}

Li, Qinhan ^{[1
]}

Ma, Siyu ^{[1
]}

Pan, Qi ^{[1
]}

Lin, Jiayi ^{[1
]}

Jiang, Nan ^{[1
]}

Ma, Jinghua ^{[1
]}

Li, Yongbo ^{[1
]}

Hou, Yannan ^{[1
]}

Zhi, Xiuling ^{[1
]}

Jiang, Lindi ^{[1
]}

Qu, Lefeng ^{[2
]}

Osto, Elena ^{[3
]}

Wang, Xinhong ^{[1
]}

Wei, Xiangxiang ^{[1
,4
,5
]}

Meng, Dan ^{[1
]}

机构：

[1] Fudan Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, 130 Dongan Rd, Shanghai 200032, Peoples R China

[2] Naval Med Univ, Changzheng Hosp, Dept Vasc & Endovascular Surg, Shanghai 200003, Peoples R China

[3] Med Univ Graz, Otto Loewi Res Ctr Vasc Biol, Div Physiol & Pathophysiol, Graz, Austria

[4] Shanghai Med Coll, 446 Zhaojiabang Rd, Shanghai 200032, Peoples R China

[5] Zhongshan Hosp Immunotherapy Translat Res Ctr, 446 Zhaojiabang Rd, Shanghai 200032, Peoples R China

来源：

CELL REPORTS | 2023年 / 42卷 / 12期

关键词：

ARGININE METHYLTRANSFERASE; IN-VITRO; CARM1; GENERATION; LINEAGE; BINDING; ATHEROSCLEROSIS; PLURIPOTENCY; GENE; MAF;

D O I：

10.1016/j.celrep.2023.113468

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：18

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