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Single Cell Transcriptional Sequencing of Epicardium-Derived Cells and Endothelial Cells During Cardiac Development

ABSTRACT: The goal of this study was to perform transcriptional profiling of single epicardium-derived cells during early cardiac development. Epicardium enriched Wilms Tumor Gene 1 (Wt1) genetic lineage tracing mouse line (Wt1CreERT2/+; R26mTmG) was utilized to collect fluorescently labeled epicardial cells at embryonic day (E) 12.5 and following epicardial-to-mesenchymal transition at E16.5. Additionally, single cell transcriptional profiling was performed in endothelial cells that were collected from Wt1CreERT2/+ mice and Wt1CreERT2/+;MRTF-A-/-;MRTF-Bflox/flox to generate myocardin-related transcription factor A and B gene deletions in the epicardium and evaluate the impact of deleting a mechanosensitive gene program on coronary vasculature development at E14.5. This transcriptional data provides a resource to determine relative mRNA changes in epicardium-derived cells and endothelial cells during significant stages of cardiac development.

ORGANISM(S): Mus musculus

PROVIDER: GSE154715 | GEO | 2021/05/27

REPOSITORIES: GEO

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scRNA-seq of E15.5 epicardium and epicardium-derived cells

Project description:The embryonic epicardium provides a source of multipotent progenitors for cardiac lineages, including pericytes, fibroblasts and smooth muscle cells. However, it remains unclear if the epicardium comprises of heterogeneous progenitors or if epicardial cells are multipotent. Using scRNA-seq, we analysed the expression profile of epicardial and epicardial-derived cells at E15.5 and found no evidence of discrete epicardial sub-compartments. Our findings also support the notion that epicardial fate is specified after epithelial-mesenchymal transition, not pre-determined.

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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, 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.

2020-01-20 | GSE121750 | GEO

Nonmuscle myosin IIB regulates epicardial integrity and epicardium-derived mesenchymal cell maturation

Project description:Nonmuscle myosin IIB (NMIIB; heavy chain encoded by MYH10) is essential for cardiac myocyte cytokinesis. The role of NMIIB in other cardiac cells is not known. Here, we show that NMIIB is required in epicardial formation and functions to support myocardial proliferation and coronary vessel development. Ablation of NMIIB in epicardial cells results in disruption of epicardial integrity with a loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial cells from the myocardium. NMIIB-knockout and blebbistatin-treated epicardial explants demonstrate impaired mesenchymal cell maturation during epicardial epithelial-mesenchymal transition. This is manifested by an impaired invasion of collagen gels by the epicardium-derived mesenchymal cells and the reorganization of the cytoskeletal structure. Although there is a marked decrease in the expression of mesenchymal genes, there is no change in Snail (also known as Snai1) or E-cadherin expression. Studies from epicardium-specific NMIIB-knockout mice confirm the importance of NMIIB for epicardial integrity and epicardial functions in promoting cardiac myocyte proliferation and coronary vessel formation during heart development. Our findings provide a novel mechanism linking epicardial formation and epicardial function to the activity of the cytoplasmic motor protein NMIIB.

2017-07-21 | GSE101701 | GEO

Comparing a timecourse of hESC-epicardium differentiation with single-cell adult and foetal human epicardium as part of the study: A single-cell comparison of adult and foetal human epicardium defines the age-associated changes in epicardial activity

Project description:This study is associated with the GEO accession GSE216019. Abstract from article: Re-activating quiescent adult epicardium represents a potential therapeutic approach for human cardiac regeneration. However, the exact molecular differences between inactive adult and active foetal epicardium are not known. Here, we combined foetal and adult human hearts for the first time using single-cell and single-nuclei RNA sequencing, and compared epicardial cells from both stages. We found a migratory fibroblast-like epicardial population only in the foetal heart and foetal epicardium expressed angiogenic gene programs, while the adult epicardium was solely mesothelial and immune-responsive. Furthermore, we predicted that adult hearts may still receive foetal epicardial paracrine communication, including WNT-signalling with endocardium, reinforcing the validity of regenerative strategies that administer or reactivate epicardial cells in situ. Finally, we explained graft efficacy of our human embryonic stem-cell derived epicardium model, by noting its similarity to human foetal epicardium. Overall, our study defines epicardial programs of regenerative angiogenesis absent in adult hearts, contextualises animal studies, and defines epicardial endpoints required for effective human heart regeneration.

2022-10-31 | GSE216177 | GEO

Genome-wide analysis of epicardial gene expression in E11.5 mouse hearts

Project description:Identification of epicardium-enriched genes in the embryonic heart. The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in re-activation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration. Total RNA obtained from lacZ-positive epicardial cells isolated from the E11.5 Tcf21lacZ hearts compared to total dissociated heart cells

2012-11-01 | E-GEOD-41959 | biostudies-arrayexpress

A single-cell comparison of adult and foetal human epicardium defines the age-associated changes in epicardial activity

Project description:Re-activating quiescent adult epicardium represents a potential therapeutic approach for human cardiac regeneration. However, the exact molecular differences between inactive adult and active foetal epicardium are not known. Here, we combined foetal and adult human hearts for the first time using single-cell and single-nuclei RNA sequencing, and compared epicardial cells from both stages. We found a migratory fibroblast-like epicardial population only in the foetal heart and foetal epicardium expressed angiogenic gene programs, while the adult epicardium was solely mesothelial and immune-responsive. Furthermore, we predicted that adult hearts may still receive foetal epicardial paracrine communication, including WNT-signalling with endocardium, reinforcing the validity of regenerative strategies that administer or reactivate epicardial cells in situ. Finally, we explained graft efficacy of our human embryonic stem-cell derived epicardium model, by noting its similarity to human foetal epicardium. Overall, our study defines epicardial programs of regenerative angiogenesis absent in adult hearts, contextualises animal studies, and defines epicardial states required for effective human heart regeneration.

2022-10-31 | GSE216019 | GEO

EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scRNA-Seq]

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2023-02-05 | GSE196513 | GEO

EPICARDIOID SINGLE-CELL GENOMICS UNCOVER PRINCIPLES OF HUMAN EPICARDIUM BIOLOGY IN HEART DEVELOPMENT AND DISEASE [scATAC-Seq]

2023-02-05 | GSE196512 | GEO

An injury-associated transient progenitor state in the epicardium mediates heart regeneration

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2022-11-22 | GSE202836 | GEO

Genome-wide analysis of epicardial gene expression in E11.5 mouse hearts

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