Epigenetic landscape reveals MECOM as an endothelial lineage regulator.
Epigenetic landscape reveals MECOM as an endothelial lineage regulator.
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DOI：
10.1038/s41467-023-38002-w
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发表时间：
2023-04-25
影响因子：
16.6
通讯作者：
Zhang, Lili
中科院分区：
文献类型：
--
作者：
Lv, Jie;Meng, Shu;Gu, Qilin;Zheng, Rongbin;Gao, Xinlei;Kim, Jun-dae;Chen, Min;Xia, Bo;Zuo, Yihan;Zhu, Sen;Zhao, Dongyu;Li, Yanqiang;Wang, Guangyu;Wang, Xin;Meng, Qingshu;Cao, Qi;Cooke, John P.;Fang, Longhou;Chen, Kaifu;Zhang, Lili
全面了解血管内皮细胞的特性将促进心血管再生医学的发展。最近的研究发现，独特的表观遗传特征优先调控细胞身份基因。因此，我们系统地研究了内皮细胞谱系的表观遗传学图景，并确定Mecom是作为内皮细胞谱系调节因子的领先候选者。单细胞RNA-Seq分析证实，Mecom阳性细胞仅在来源于诱导的多能干细胞的真正内皮细胞的细胞团中富含。我们的实验表明，Mecom耗尽会损害人内皮细胞的分化、功能和斑马鱼血管生成。通过对Hi-C、DNase-Seq、ChIP-Seq和RNA-Seq数据的综合分析，我们发现Mecom结合了形成染色质环的增强子来调节内皮细胞识别基因。进一步，我们确定并验证了血管内皮生长因子信号通路是Mecom的一个关键靶点。我们的工作为细胞特性的表观遗传调控提供了重要的见解，并揭示了Mecom作为内皮细胞谱系调节因子的作用。血管发育错误与几种先天缺陷有关。在这里，他们系统地研究了内皮细胞谱系的表观遗传格局，发现Mecom缺失会损害内皮细胞的分化和血管生成。
A comprehensive understanding of endothelial cell lineage specification will advance cardiovascular regenerative medicine. Recent studies found that unique epigenetic signatures preferentially regulate cell identity genes. We thus systematically investigate the epigenetic landscape of endothelial cell lineage and identify MECOM to be the leading candidate as an endothelial cell lineage regulator. Single-cell RNA-Seq analysis verifies that MECOM-positive cells are exclusively enriched in the cell cluster of bona fide endothelial cells derived from induced pluripotent stem cells. Our experiments demonstrate that MECOM depletion impairs human endothelial cell differentiation, functions, and Zebrafish angiogenesis. Through integrative analysis of Hi-C, DNase-Seq, ChIP-Seq, and RNA-Seq data, we find MECOM binds enhancers that form chromatin loops to regulate endothelial cell identity genes. Further, we identify and verify the VEGF signaling pathway to be a key target of MECOM. Our work provides important insights into epigenetic regulation of cell identity and uncovered MECOM as an endothelial cell lineage regulator. Errors in vascular development are associated with several congenital defects. Here they systematically investigated the epigenetic landscape of the endothelial lineage and found that MECOM depletion impairs endothelial cell differentiation and angiogenesis.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
16.6
作者：
Dejana E;Hirschi KK;Simons M
通讯作者：
Simons M
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Benayoun BA;Pollina EA;Ucar D;Mahmoudi S;Karra K;Wong ED;Devarajan K;Daugherty AC;Kundaje AB;Mancini E;Hitz BC;Gupta R;Rando TA;Baker JC;Snyder MP;Cherry JM;Brunet A
通讯作者：
Brunet A