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Functional heterogeneity within the developing zebrafish epicardium

ABSTRACT: Functional heterogeneity within the developing zebrafish epicardium

PROVIDER: PRJNA498309 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8106260_1.fastq.gz	Fastqsanger.gz
	SRR8106260_2.fastq.gz	Fastqsanger.gz
	SRR8106270_1.fastq.gz	Fastqsanger.gz
	SRR8106270_2.fastq.gz	Fastqsanger.gz
	SRR8106280_1.fastq.gz	Fastqsanger.gz

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Functional heterogeneity within the developing zebrafish epicardium

Project description:The epicardium is essential during cardiac development, homeostasis and repair and yet fundamental insights into its underlying cell biology, notably epicardium formation, lineage heterogeneity and functional cross-talk with other cell types in the heart, is currently lacking. In this study, we investigated epicardial heterogeneity and the functional diversity of discrete epicardial subpopulations in the developing zebrafish heart. Single-cell RNA-sequencing uncovered three epicardial subpopulations with specific genetic programmes and distinctive spatial distribution within the developing heart. Perturbation of unique gene signatures uncovered distinct functions associated with each subpopulation and established novel epicardial roles in cell adhesion, migration, and chemotaxis as a mechanism for recruitment of leukocytes into the heart. This work elucidates the mutual spatiotemporal relationships between different epicardial subpopulations and assigns unique function to each during cardiac development. Understanding which mechanisms cells employ to establish a functional epicardium and to communicate with other cardiovascular cell types during development will bring us closer to repairing cellular relationships that are disrupted during cardiovascular disease.

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Project description:The epicardium is essential during cardiac development, homeostasis, and repair, and yet fundamental insights into its underlying cell biology, notably epicardium formation, lineage heterogeneity, and functional cross-talk with other cell types in the heart, are currently lacking. In this study, we investigated epicardial heterogeneity and the functional diversity of discrete epicardial subpopulations in the developing zebrafish heart. Single-cell RNA sequencing uncovered three epicardial subpopulations with specific genetic programs and distinctive spatial distribution. Perturbation of unique gene signatures uncovered specific functions associated with each subpopulation and established epicardial roles in cell adhesion, migration, and chemotaxis as a mechanism for recruitment of leukocytes into the heart. Understanding which mechanisms epicardial cells employ to establish a functional epicardium and how they communicate with other cardiovascular cell types during development will bring us closer to repairing cellular relationships that are disrupted during cardiovascular disease.

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Project description:Epicardial cells can undergo epithelium-to-mesenchymal transition (EMT) upon which the epicardium-derived cells (EPDCs) migrate into the myocardium and deliver growth factors or differentiate into smooth muscle cells or fibroblasts. The cell fate of EPDCs has been proposed to be determined by the persistence of subpopulations found in the proepicardial organ, but findings regarding this epicardial heterogeneity have been inconsistent. In the human heart, the composition of the developing epicardium is largely unknown. Here we performed a direct analysis of the human fetal epicardium through single cell RNA sequencing to investigate its composition and to search for regulators of developmental processes

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