Dgcr8 deletion in the primitive heart uncovered novel microRNA regulating the balance of cardiac-vascular gene program

作     者：Xi Chen Lin Wang Rujin Huang Hui Qiu Peizhe Wang Daren Wu Yonglin Zhu Jia Ming Yangming Wang Jianbin Wang Jie Na 

作者机构：Center for Stem Cell Biology and Regenerative MedicineSchool of MedicineTsinghua UniversityBeijing 100084China Beijing Key Laboratory of Cardiometabolic Molecular MedicineInstitute of Molecular MedicinePeking UniversityBeijing 100871China School of Life SciencesTsinghua UniversityBeijing 100084China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2019年第10卷第5期

页      面：327-346页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：the National Key R&D Program of China,grants 2017YFA0102802 and 2016YFC0900100 to J.Na and J.Wang the National Natural Science Foundation of China(NSFC)grants 91740115,21675098 and 31471222 to J.Na,J.Wang and Y.Wang the National Basic Research Program of China,grant 2012CB966701 to J.Na the funding from Tsinghua-Peking Center for Life Sciences and core facilities of Tsinghua-Peking Center for Life Sciences 

主　　题：microRNA Dgcr8 Cardiovascular progenitor cells miRNA-541 Single cell RNA sequencing 

摘      要：Primitive mammalian heart transforms from a single tube to a four-chambered muscular organ during a short developmental *** found that knocking out global microRNA by deleting Dgcr8 microprocessor in Mespl cardiovascular progenitor cells lead to the formation of extremely dilated and enlarged heart due to defective cardiomyocyte(CM)*** analysis revealed unusual upregulation of vascular gene expression in Dgcr8 cKO *** cell RNA sequencing study further confirmed the increase of angiogenesis genes in single Dgcr8 cKO *** also performed global microRNA profiling of E9.5 heart for the first time,and identified that miR-541 was transiently highly expressed in E9.5 ***,introducing miR-541 back into microRNA-free CMs partially rescued their defects,downregulated angiogenesis genes and significantly upregulated cardiac ***,miR-541 can target Ctgf and inhibit endothelial *** results suggest that micro-RNAs are required to suppress abnormal angiogenesis gene program to maintain CM differentiation.