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 Mespl 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 micro-RNAs are required to suppress abnormal angiogenesis gene program to maintain CM differentiation.
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.
