title: Hypoxia induced the differentiation of Tbx18-positive epicardial cells to CoSMCs.
abstract: Understanding the origin and differentiation mechanism of coronary vascular smooth muscle cells (CoSMCs) is very important to cardiovascular biology. The early cardiovascular system is formed in a hypoxic microenvironment, and Tbx18-positive epicardial cells are a source of CoSMCs. However, the effects of hypoxia on the differentiation of Tbx18-positive epicardial cells to CoSMCs and the primary regulatory mechanism are insufficiently understood. Using Tbx18:Cre/R26R(EYFP/LacZ) fate-tracing mice, we cultured highly purified Tbx18-positive epicardial cells. We further showed that hypoxia induced Tbx18-positive epicardial cells to differentiate into CoSMCs and promoted the epithelial-mesenchymal transition (EMT) process of the cells in vitro. The induction of differentiation was primarily achieved via the hypoxia inducible factor-1α (HIF-1α)-mediated effects exerted on Snail. Using a cell migration assay, we showed that hypoxia enhanced the motility of Tbx18-positive epicardial cells. By constructing a hypoxic model of the embryonic epicardium in vivo, we showed that hypoxia led to premature in situ differentiation of Tbx18-positive epicardial cells to CoSMCs. Furthermore, hypoxia was sufficient to induce Snail expression in Tbx18-positive epicardial cells in vivo. Our study suggests that hypoxia intervention was sufficient to induce the differentiation of Tbx18-positive epicardial cells to CoSMCs. Furthermore, this differentiation was achieved primarily via HIF-1α-mediated regulation of Snail.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Songbai
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: She
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D010496:Pericardium / Q000166:cytology*; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071250:Snail Family Transcription Factors; D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse