Comparison of primary epicardium explant derived CDCs and primary Epicardial cells
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PROVIDER: PRJNA782323 | ENA |
REPOSITORIES: ENA
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Project description:The analysis showed differences of transcriptomes between primary epicardium explant derived CDCs and primary Epicardial cells directly isolated from the heart epicardium.SB-431542 was an effective TGF-b pathway inhibitor that could obviously inhibit the epicardial cells Epithelial-mesenchymal transition. SB-432542 treatment could produce some epithelial clones in the CDCs,which showed epicardiac specific expression profile, compared with the CDCs.
2022-02-18 | GSE189275 | GEO
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
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
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
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.
2020-04-30 | GSE145832 | GEO
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
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
Project description:The epicardium is a mesothelial layer covering the myocardium and contributes to different cardiac lineage descendants during cardiogenesis. Fine-tuned balanced signaling defines epicardial specification and regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) by epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial cell function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated embryonic epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a novel biomarker defining lineage specification in human developing epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results demonstrate the production and enrichment of hiPSC-derived epicardial cells via the tracing of CDH18 expression, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine.
2022-02-18 | GSE165450 | GEO
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.
2012-11-01 | GSE41959 | GEO
Project description:Adult zebrafish regenerate heart muscle after severe cardiac damage without significant scarring. The epicardium, a mesothelial cell sheet covering the vetebrate heart, is activated by injury and supports muscle regeneration through paracrine effects and as a source of multipotent cells. The understudied cellular heterogeneity of the adult epicardium during heart regeneration has constrained the effort in mobilizing the epicardium for heart repair. To dissect epicardial cell states and the underlying mechanisms that lead to successful heart regeneration in zebrafish, we performed single-cell RNA-sequencing of isolated epicardial cells from the regenerating adult heart and revealed their dynamic cellular heterogeneity. We defined the epithelial and mesenchymal layers of the epicardium and identified a transiently activated epicardial progenitor cell (aEPC) subpopulation that expresses aldh1a2, ptx3a, col12a1b and marcksb. Upon heart amputation injury, aEPCs emerge from the existing epicardial cells, migrate to enclose the wound, and disappear as regeneration progresses. Genetic lineage tracing combined with modified RNA labelling confirmed an epithelial-mesenchymal transition (EMT) process of aEPCs and their differentiations to pdgfrb+ mural cells and pdgfra+hapln1a+ mesenchymal fibroblast-like cells that support heart regeneration. Genetic ablation of aEPCs blocked wound closure of the injured ventricle, suppressed cardiomyocyte proliferation, and disrupted heart regeneration. Our findings define a transient progenitor state of the adult epicardium that is an indispensable driver of zebrafish heart regeneration and identified ptx3a as a regeneration-specific non-ontogenetic regulator of the epicardium.
2022-11-22 | GSE202836 | GEO