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Uncovering the epigenomic determinants of kidney vascular development [scATAC-seq]

ABSTRACT: Uncovering the epigenomic determinants of kidney vascular development [scATAC-seq]

PROVIDER: PRJNA904336 | ENA |

REPOSITORIES: ENA

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Uncovering the epigenomic determinants of kidney vascular development

Project description:Uncovering the epigenomic determinants of kidney vascular development

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Uncovering the epigenomic determinants of kidney vascular development [scRNA-seq]

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Uncovering the epigenomic determinants of kidney vascular development [scATAC-seq]

Project description:Renin cells are essential for survival. They control the morphogenesis of the kidney arterioles, and the composition and volume of our extracellular fluid, arterial blood pressure, tissue perfusion, and oxygen delivery. Renin cells and associated arteriolar cells descend from FoxD1+ progenitor cells. The chromatin states and transcription factors that determine the differentiation of these cells into those that compose the kidney vasculature are unknown. To answer these questions, we isolated progenitors and their descendants at different embryonic and postnatal stages, and using integrated scRNA-seq and scATAC-seq established the developmental trajectory that leads to the mosaic of cells that compose the kidney arterioles. We constructed a single-cell atlas of chromatin accessibility and gene expression profiles-including the critical transcription factors that determine the identity and fate of the mosaic of cells that occur during kidney vascular development. Furthermore, we identified the factors that determine the elusive, myo-endocrine adult renin-secreting juxtaglomerular cell.

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Uncovering the epigenomic determinants of kidney vascular development [scRNA-seq]

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Uncovering the epigenomic determinants of kidney vascular development

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scATAC-seq of mouse Plasmodium-specific CD4+ T cells

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Project description:The kidney vasculature is specialized to filter waste products from the blood, regulate blood pressure, and balance electrolytes. Although recent advances in stem cell studies have enabled the partial generation of kidney tissues in vitro, recapitulating the complex vascular structures of the kidney remains a daunting task. The molecular pathways that specify and sustain kidney vascular heterogeneity to perform these diverse tasks are not well characterized. Here, we have employed high throughput bulk and single-cell RNA sequencing of the non-lymphatic vasculature of the kidney to uncover the progression of pathways that dictate the developmental transition of nephrogenesis and vascular zonation from embryos to adulthood. We show that glomeruli and its associated vessels, manifest vascular-specific signatures expressing defined transcription factors, ion channels, solute transporters, and paracrine factors choreographing kidney functions. Notably, the ontology of the glomerulus coincides with induction of several unique transcription factors, including Tbx3, Gata5, Prdm1, and Pbx1. Selective deletion of Tbx3 in endothelial cells result in glomerular hypoplasia, microaneurysms and regressed fenestrations leading to fibrosis. Unraveling the molecular determinants of kidney vascular signatures will lay the foundation for rebuilding nephrons and understanding the pathogenesis of kidney diseases.

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Project description:Temporal and functional determinants of intra-hepatic vascular homeostatic specialization

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