ScRNA-seq of 50 and 80 hpf isolated zebrafish hearts
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE242483 | GEO | 2024/02/13
REPOSITORIES: GEO
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Project description:scRNA-seq of 50 and 80 hpf isolated zebrafish hearts
| PRJNA1013567 | ENA
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Project description:Valvular heart disease presents a significant health burden, yet advancements in valve biology and novel therapeutics have been hindered by the lack of accessibility to human valve cells. In this study, we have developed a scalable and feeder-free method to differentiate human induced pluripotent stem cells (iPSCs) into endocardial cells. Importantly, we show that these endocardial cells are transcriptionally and phenotypically distinct from vascular endothelial cells and can be directed to undergo endothelial-to-mesenchymal transition (EndMT) to generate cardiac valve cell populations. Following this, we identified two distinct populations—one population undergoes EndMT to become valvular interstitial cells (VICs), while the other population reinforces their endothelial identity to become valvular endothelial cells (VECs). We then characterized our iPSC-derived cell populations and identified putative markers for these populations through bulk RNAseq transcriptome analyses. Lastly, we validated our VIC and VEC populations by comparing our transcriptomic data to pseudobulk data generated from single-cell RNAseq of normal valve tissue from a 15-week-old human fetus. By increasing the accessibility to these cell populations, we aim to accelerate discoveries for cardiac valve biology and disease.
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Project description:One third of cardiac congenital diseases affect cardiac valves. Genetically modifiedmice have advancedourunderstandingof valve development and related pathologies. However, little is known with regard tohuman valve development.We aimed to derive a novel human pluripotent stem cellmodel in order to decode the early steps of human valvulogenesis.Human MesP1+mesodermal cells were differentiated toward the fate of second heart field progenitors and then to a selected population of pre-valvular endocardial cells. Gene arrays revealed that these human prevalvular cells (HPVC) express patterns of genes similar to those expressed in theatrioventricular canal (AVC) endocardium of E9.0 mouse embryos. In mice this developmental time precedes endocardial mesenchymal transition (EndoMT),which is required for mature valve formation.HPVC treated with BMP2, cultured onto chick or mouse AVC cushions, or transplanted into the outflow tract or AVC of embryonic chick and mouse hearts, underwent EndoMTin both a Notch-dependent and independent-manner and expressed markers of valve mesenchymal cells and fibroblasts.Similar to the previously described valve interstitial cells (VICs), HPVC also differentiate into tendinous/chondrogenic cells. Our study indicates thathuman pluripotent stem cells canrecapitulate early valvulogenesis and thus provide a powerful model to further decipher the origin and lineage contributionof different valvular cell typesin humans.
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