Coordination of endothelial cell positioning and fate specification by the epicardium.
Coordination of endothelial cell positioning and fate specification by the epicardium.
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DOI：
10.1038/s41467-021-24414-z
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发表时间：
2021-07-06
影响因子：
16.6
通讯作者：
Small EM
中科院分区：
文献类型：
--
作者：
Quijada P;Trembley MA;Misra A;Myers JA;Baker CD;Pérez-Hernández M;Myers JR;Dirkx RA Jr;Cohen ED;Delmar M;Ashton JM;Small EM
完整的冠状动脉血管系统的组织需要根据未成熟内皮细胞（EC）在心脏内的定位将其指定为动脉和静脉命运。目前还不清楚空间信息如何控制EC的身份和行为。在这里，我们使用单细胞RNA测序在关键的发展时间点，询问冠状动脉血管的图案和成熟的细胞贡献。我们进行转录分析，以确定一个异质性人口的心外膜衍生细胞（EPDCs）表达独特的趋化因子的签名。我们确定了一个人口的Slit 2 + EPDCs出现后上皮间质转化（EMT），我们称之为血管路标细胞。我们表明，引导衍生的趋化因子，如Slit 2的表达诱导心外膜细胞进行EMT，而间皮衍生的趋化因子沉默。我们证明，心外膜特异性删除心肌相关的转录因子在小鼠胚胎中破坏了关键的指导线索的表达和改变EPDC-EC信号，导致持久的不成熟的血管生成EC身份和不适当的积累EC的心外膜表面。我们的研究表明，EC寻路和命运的规范是由一个共同的机制控制，并指导旁分泌信号从EPDCs连接心外膜EMT EC定位和命运的规范在发展中的心脏。目前尚不清楚空间信息如何控制发育中的心脏内皮细胞的身份和行为。在这里，作者在小鼠的关键发育时间点进行单细胞RNA测序，以询问细胞对心外膜中冠状血管图案和成熟的贡献。
The organization of an integrated coronary vasculature requires the specification of immature endothelial cells (ECs) into arterial and venous fates based on their localization within the heart. It remains unclear how spatial information controls EC identity and behavior. Here we use single-cell RNA sequencing at key developmental timepoints to interrogate cellular contributions to coronary vessel patterning and maturation. We perform transcriptional profiling to define a heterogenous population of epicardium-derived cells (EPDCs) that express unique chemokine signatures. We identify a population of Slit2+ EPDCs that emerge following epithelial-to-mesenchymal transition (EMT), which we term vascular guidepost cells. We show that the expression of guidepost-derived chemokines such as Slit2 are induced in epicardial cells undergoing EMT, while mesothelium-derived chemokines are silenced. We demonstrate that epicardium-specific deletion of myocardin-related transcription factors in mouse embryos disrupts the expression of key guidance cues and alters EPDC-EC signaling, leading to the persistence of an immature angiogenic EC identity and inappropriate accumulation of ECs on the epicardial surface. Our study suggests that EC pathfinding and fate specification is controlled by a common mechanism and guided by paracrine signaling from EPDCs linking epicardial EMT to EC localization and fate specification in the developing heart. It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.
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影响因子：
9.8
作者：
Franco CA;Jones ML;Bernabeu MO;Geudens I;Mathivet T;Rosa A;Lopes FM;Lima AP;Ragab A;Collins RT;Phng LK;Coveney PV;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
7.7
作者：
Franco CA;Jones ML;Bernabeu MO;Vion AC;Barbacena P;Fan J;Mathivet T;Fonseca CG;Ragab A;Yamaguchi TP;Coveney PV;Lang RA;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
21.3
作者：
Jones CA;Nishiya N;London NR;Zhu W;Sorensen LK;Chan AC;Lim CJ;Chen H;Zhang Q;Schultz PG;Hayallah AM;Thomas KR;Famulok M;Zhang K;Ginsberg MH;Li DY
通讯作者：
Li DY
影响因子：
16.6
作者：
Fang JS;Coon BG;Gillis N;Chen Z;Qiu J;Chittenden TW;Burt JM;Schwartz MA;Hirschi KK
通讯作者：
Hirschi KK
影响因子：
11.8
作者：
Cavallero, Susana;Shen, Hua;Yi, Christopher;Lien, Ching-Ling;Kumar, S. Ram;Sucov, Henry M.
通讯作者：
Sucov, Henry M.