机构:[1]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China[2]MOE Key Laboratory of Contemporary Anthropology at School of Life Sciences, Fudan University, Shanghai 200438, China[3]State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai 200438, China[4]Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, China首都医科大学附属安贞医院
Recent evidence has shown that cardiomyocytes (CMs) can proliferate at a low level after myocardial infarction (MI), but it is insufficient to reestablish heart function. Several microRNAs (miRNAs) have been proven to sufficiently induce rodent CM proliferation. However, whether miRNAs identified in rodents can promote human CM proliferation is unknown due to the poorly conserved functions of miRNAs among species. In the present study, we demonstrate that i) expression of microRNA-302d (miR-302d) decreased significantly during CM differentiation from human pluripotent stem cells (hPSCs) from day 4 to day 18; ii) miR-302d efficiently promoted proliferation of hPSC-derived CMs; iii) miR-302d promoted CM proliferation by targeting LATS2 in the Hippo pathway; and iv) RNA-sequencing analysis revealed that overexpression of miR-302d induced changes in gene expression, which mainly converged on the cell cycle. Our study provides further evidence for the therapeutic potential of miR-302d.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81870199]; National Basic Research Program of ChinaNational Basic Research Program of China [2015CB943300]; Foundation for Innovative Research Group of the National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31521003]; Opening Program 2018 of the State Key Laboratory of Genetic Engineering [SKLGE1809]
第一作者机构:[1]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China
通讯作者:
通讯机构:[1]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China[2]MOE Key Laboratory of Contemporary Anthropology at School of Life Sciences, Fudan University, Shanghai 200438, China
推荐引用方式(GB/T 7714):
Fei Xu,Jingcheng Yang,Jun Shang,et al.MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting LATS2 in the Hippo pathway[J].CLINICAL SCIENCE.2019,133(13):1387-1399.doi:10.1042/CS20190099.
APA:
Fei Xu,Jingcheng Yang,Jun Shang,Feng Lan,Miaomiao Li...&Junbo Ge.(2019).MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting LATS2 in the Hippo pathway.CLINICAL SCIENCE,133,(13)
MLA:
Fei Xu,et al."MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting LATS2 in the Hippo pathway".CLINICAL SCIENCE 133..13(2019):1387-1399