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

被引：13

作者：

Chen, Xi ^{[1
]}

Wang, Lin ^{[1
]}

Huang, Rujin ^{[1
]}

Qiu, Hui ^{[1
]}

Wang, Peizhe ^{[1
]}

Wu, Daren ^{[2
]}

Zhu, Yonglin ^{[1
]}

Ming, Jia ^{[1
]}

Wang, Yangming ^{[2
]}

Wang, Jianbin ^{[3
]}

Na, Jie ^{[1
]}

机构：

[1] Tsinghua Univ, Sch Med, Ctr Stem Cell Biol & Regenerat Med, Beijing 100084, Peoples R China

[2] Peking Univ, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China

[3] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

来源：

PROTEIN & CELL | 2019年 / 10卷 / 05期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

microRNA; Dgcr8; Cardiovascular progenitor cells; miRNA-541; Single cell RNA sequencing; TISSUE GROWTH-FACTOR; MIGRATION; PROLIFERATION; ANGIOGENESIS; EXPRESSION; CELLS;

D O I：

10.1007/s13238-018-0572-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Primitive mammalian heart transforms from a single tube to a four-chambered muscular organ during a short developmental window. We found that knocking out global microRNA by deleting Dgcr8 microprocessor in Mesp1 cardiovascular progenitor cells lead to the formation of extremely dilated and enlarged heart due to defective cardiomyocyte (CM) differentiation. Transcriptome analysis revealed unusual upregulation of vascular gene expression in Dgcr8 cKO hearts. Single cell RNA sequencing study further confirmed the increase of angiogenesis genes in single Dgcr8 cKO CM. We 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 hearts. Interestingly, introducing miR-541 back into microRNA-free CMs partially rescued their defects, downregulated angiogenesis genes and significantly upregulated cardiac genes. Moreover, miR-541 can target Ctgf and inhibit endothelial function. Our results suggest that microRNAs are required to suppress abnormal angiogenesis gene program to maintain CM differentiation.

引用

页码：327 / 346

页数：20

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