Single-cell analysis of human fetal epicardium reveals its cellular composition and identifies CRIP1 as a modulator of EMT
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PROVIDER: PRJNA882054 | ENA |
REPOSITORIES: ENA
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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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Project description:The epicardium plays an essential role in cardiogenesis by providing cardiac cell types and paracrine cues to the developing myocardium. The human adult epicardium is quiescent, but recapitulation of developmental features may contribute to adult cardiac repair. The cell fate of epicardial cells is proposed to be determined by the developmental persistence of specific subpopulations. Reports on this epicardial heterogeneity have been inconsistent, and data regarding the human developing epicardium are scarce. Here we specifically isolated human fetal epicardium and used single-cell RNA sequencing to define its composition and to identify regulators of developmental processes. Few specific subpopulations were observed, but a clear distinction between epithelial and mesenchymal cells was present, resulting in novel population-specific markers. Additionally, we identified CRIP1 as a previously unknown regulator involved in epicardial epithelial-to-mesenchymal transition. Overall, our human fetal epicardial cell-enriched dataset provides an excellent platform to study the developing epicardium in great detail.
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Project description:Here we characterize human fetal cardiac lymphatic vessel development and reveal a new role for cells that reside in the epicardium as a source of progenitors involved in cardiac lymphatic differentiation. The single nuclei (sn) Multiome data of the human heart reveal the plasticity and the heterogeneity of the cardiac lymphatic endothelium. We have captured nuclei from a novel population of lymphatic progenitors in the epicardium and performed an integrative snRNAseq and snATACseq analysis to define the gene expression and gene regulatory landscape of these cardiac lymphatic cells in human fetal hearts.
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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.
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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:Single nuclei RNAseq of human fetal cardiac cells from the epicardium of 10PCW and 11PCW
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Project description:The HH16/17 chicken proepicardium (PE) gives rise to the embryonic epicardium (Epi) which significantly contributes formation of the coronary vasculature during cardiac development. In contrast to explanted Epi cells, explanted PE cells can undergo differentiation into a cardiac myocyte phenotype. In order to assess which genes are associated with PE differentiation into distinc cellular lineages, two interconnented microarray gene-expression series were performed. 1: Gene-expression profiles at 12, 24, 36, 48, 60, 72 and 120 hours during cardiac myocyte differentiation from including the HH16/17 PE (t0h) were determined by hybridizing Cy3 and Cy5 labelled amplified RNA to the ArkGen 20K oligo arrays in a 2-color looped experiment design, i.e., hybridization of successive time-points per array, including dye swaps, resulting in four technical replicates for each time point. 2: Gene expression changes during normal embryonic Epi maturation were assess by hybridizing Epi from stages HH25, HH29, HH32 and HH37 in all possible pair-wise combinations, including dye-swaps, leading to 6 replicates per time point. To allow for valid comparisons between the Epi and untreated PE differentiation, these two array series were connected via hybridization of both Epi stage HH25 and HH29 with the PE explant at 48 hours in culture, with dye swaps. Keywords: time course, cardiac myocyte differentiation, embryonic coronary vessel formation, cell type comparison, mRNA expression Proepicardium to cardiac myocyte differentiation: 16 arrays for 8 time points [t0h,t12h,t24h,t36h,t48h,t60h,t72h,t120h]; successive time points hybridized per array in a loop design with dye swaps + Embryonic epicardium dfferentiation: 12 arrays for 4 time points [HH25,HH29,HH32,HH37]; all possible sample combination were hybridized with dye swaps + Epicardium to Proepicardium data connection: 4 arrays; comparing HH25 and HH29 Epicardium to t48h Proepicardium with dye swaps.
2010-12-21 | E-GEOD-13923 | biostudies-arrayexpress