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
Affiliations
Yunquan He
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Jieyu Guo
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Yueyang Yu
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Jiayu Jin
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Qingjun Jiang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China; Department of Vascular & Endovascular Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Qinhan Li
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Siyu Ma
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Qi Pan
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Jiayi Lin
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Nan Jiang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Jinghua Ma
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Yongbo Li
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Yannan Hou
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Xiuling Zhi
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Lindi Jiang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China
Lefeng Qu
Department of Vascular & Endovascular Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
Elena Osto
Division of Physiology and Pathophysiology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
Xinhong Wang
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China; Corresponding author
Xiangxiang Wei
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China; Shanghai Medical College and Zhongshan Hospital Immunotherapy Translational Research Center, 446 Zhaojiabang Road, Xuhui District, Shanghai 200032, China; Corresponding author
Dan Meng
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, 138 Yixueyuan Road, Xuhui District, Shanghai 200032, China; Corresponding author
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.
