Coordination of endothelial cell positioning and fate specification by the epicardium

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...

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Veröffentlicht in:Nature communications 2021-07, Vol.12 (1), p.4155-4155, Article 4155
Hauptverfasser: Quijada, Pearl, Trembley, Michael A., Misra, Adwiteeya, Myers, Jacquelyn A., Baker, Cameron D., Pérez-Hernández, Marta, Myers, Jason R., Dirkx, Ronald A., Cohen, Ethan David, Delmar, Mario, Ashton, John M., Small, Eric M.
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container_title Nature communications
container_volume 12
creator Quijada, Pearl
Trembley, Michael A.
Misra, Adwiteeya
Myers, Jacquelyn A.
Baker, Cameron D.
Pérez-Hernández, Marta
Myers, Jason R.
Dirkx, Ronald A.
Cohen, Ethan David
Delmar, Mario
Ashton, John M.
Small, Eric M.
description 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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subjects 13
14
14/1
38
38/32
38/39
38/91
631/114/2404
631/136/16/1986
631/136/2086/2176
631/1647/334/1874/345
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64
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Angiogenesis
Blood vessels
Chemokines
Coronary vessels
Embryos
Endothelial cells
Epicardium
Gene sequencing
Heart
Humanities and Social Sciences
Localization
Maturation
Mesenchyme
Mesothelium
multidisciplinary
Paracrine signalling
Pattern formation
Science
Science (multidisciplinary)
Signaling
Spatial data
Specifications
Transcription factors
title Coordination of endothelial cell positioning and fate specification by the epicardium
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