Hapln1 defines an epicardial cell subpopulation that establishes cardiogenic hotspots during heart morphogenesis and regeneration
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PROVIDER: PRJNA723588 | ENA |
REPOSITORIES: ENA
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Project description:The epicardium, a thin mesothelial tissue layer that encompasses the heart, is a dynamic structure that is essential for cardiac regeneration in species with elevated regenerative capacity like zebrafish. To dissect epicardial cell states and associated pro-regenerative functions, we performed single-cell RNA-sequencing and identified 7 epicardial cell clusters in adult zebrafish, with 3 of these clusters enhanced during regeneration. ECM components encoded by hapln1 paralogs label an enriched epicardial cell type that accumulates and encloses dedifferentiated and proliferating cardiomyocytes during regeneration. Genetic inactivation of hapln1b, or induced genetic depletion of hapln1a-expressing cells, disrupted cardiomyocyte proliferation and heart regeneration. hapln1a+ cells first emerge at the juvenile stage, when they associate with and are required for cardiogenic foci that direct growth of the juvenile heart. Our findings identify a subset of epicardial cells that emerges in post-embryonic animals and sponsors regions of active cardiomyogenesis during heart growth and regeneration
2022-06-17 | GSE172511 | GEO
Project description:Rationale: Epicardium-derived cells (EPDC) are formed in response to myocardial infarction and recapitulate an embryonic program that is likely to participate in cardiac regeneration and remodeling. The existence of atrial counterparts that are potentially involved in atrial remodeling is still elusive. Objective: We have elaborated and validated techniques for the robust isolation and cultivation of atrial and ventricular EPDC from the rat heart and compared their molecular phenotype with human atrial stromal cells obtained from tissue biopsies. Methods and Results: In vitro culture revealed that rat and human cells display a similar morphology, are highly enriched for the epicardial markers WT-1 and Tbx18 throughout in vitro expansion, strongly express the stem/progenitor cell markers CD73, CD90 and, surprisingly the early and late cardiac markers Gata4, Tbx5 and troponin T. In general, these cells display a similar molecular signature - which is different from human MSC - when analyzed by FACS, immunohistochemistry and real time PCR. We also examined the cell surface proteome of human and rat EPDC using cell surface biotinylation combined with nano-liquid chromatography - mass spectrometry. Proteome analysis revealed the presence of 149 overlapping proteins and >200 species specific proteins. These proteins are preferentially involved in cardiac repair and regeneration. Conclusions: This study demonstrates that atrial stromal cells are EPDC suggesting a common epicardial precursor. Cell surface proteome analysis suggests that atrial and ventricular EPDC are likely to play an important role during atrial and ventricular remodeling.
2018-10-19 | PXD005013 | Pride
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:Single cell RNA sequencing (scRNA-Seq) is applied to charaterize the pro-epicardial cells (proEpiCs) in mouse pro-epicardial organ (PEO).
2020-04-04 | GSE148040 | 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:By contrast with mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of spared cardiomyocytes. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. While it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. In this study, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin-1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration. Deep sequencing of isolated single epicardial cells
2015-12-15 | E-GEOD-75583 | biostudies-arrayexpress
Project description:Rationale: Cardiac development is a complex process that results in the first integrated, multi-lineage embryonic tissue. Imperfect developmental progression leads to congenital heart disease, the most common birth defect with developmental corruption affecting more than 1% of all live births. Interrogation of individual genes has provided the backbone for cardiac developmental biology, yet a comprehensive transcriptome derived from natural cardiogenesis is required to establish an unbiased roadmap to gauge innate developmental milestones necessary for stem cell-based differentiation and in vitro disease modeling. Objective: Establish a contextual expression database of spatial-temporal cardiac structures, and validate a predictive tool to diagnose and predict cardiogenic outcomes from individual pluripotent stem cell lines. Methods and Results: Stage-specific cardiac structures were dissected from eight distinctive embryonic time points to produce a genome-wide expressome analysis across the spectrum of early to late cardiogenesis. Hierarchical clustering of the time course dataset demonstrated discrete gene expression profiles during natural embryonic development. In reference to the native cardiogenic expression roadmap, disruptive iPSC-derived cardiac expression profiles were revealed from pro-cardiogenic 3-factor (SOX2, OCT4, KLF4) compared to non-cardiogenic 4-factor (addition of c-MYC) reprogramming regimens upon stage-specific differentiation. Expression of cardiac-related genes from 3F-iPSC differentiated in vitro at day 0, 5, and 11 recapitulated expression of natural embryos at days 0, E7.5-E8.5, and E14.5-E18.5, respectively. In contrast, 4F-iPSC demonstrated variable gastrulation gene expression profiles beginning at day 5 of differentiation. Differential gene expression within the pluripotent ground state between the archetypical high cardiogenic potential of embryonic stem cells recapitulated in 3F-iPSC vs. the low cardiogenic potential of 4F-iPSC revealed 23 distinguishing candidate genes. Upon subsequent differentiation, cell line-specific gene expression differences were magnified to 399 genes at day 5 and 726 genes at day 11. A confirmed panel of 20 genes, differentially expressed between high and low cardiogenic cell lines, was transformed into a predictive score that was sufficient to correctly rank independent iPSC lines according to cardiogenic potential. Conclusions: Transcriptome analysis attuned to the embryonic developing heart provides a robust platform to probe coordinated cardiac specification and maturation from stem cell-based cardiogenesis model systems. Based on this genome-wide expressome roadmap, a panel of pre-cardiac genes was extracted that allowed differential prognosis of cardiogenic competency from individual reprogrammed cell lines at the pluripotent state. The overall experimental design includes 3 time points (Day0, Day5, Day11) and 3 different stem cell lines: R1 embryonic stem cells (ESCs), H9 induced pluripotent stem cells (H9-iPSCs) generated/reprogrammed by 3 transcription factors (called 3F-iPSCs), and 19BL induced pluripotent stem cells (19BL-iPSCs) generated/reprogrammed by 4 transcription factors (called 4F-iPSC). At each time point, each cell line has 3 biological replicates. In total, there are 27 samples. R1-embryonic stem cells (R1-ESCs): Day0 undifferentiated ESCs - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates. 3F-iPSC (H9 iPSCs): Day 0 undifferentiated - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates. 4F-iPSC (19BL-iPSCs): Day0 undifferentiated - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates.
2013-09-23 | E-GEOD-43197 | biostudies-arrayexpress
Project description:The goal of the present study is to determine the miRNA cargo present in epicardial extracellular vesicles. For that, epicardial cells and human primary epicardial cells were cultured. Conditioned media was isolated from mouse epicardial cells and human primary epicardial cells derived from right atrial appendages in two different states: “cobble” (inactive) cells and “spindle” (active) . RNA from EVs was isolated and sequenced to determine the miRNA content profile.
2020-11-18 | GSE161630 | GEO
Project description:This experiment aims to map SRSF3 binding to the global transcriptome in a mouse epicardial cell line
2022-12-31 | E-MTAB-11853 | biostudies-arrayexpress
Project description:Prophage-encoded hotspots of anti-phage systems
| PRJEB47940 | ENA