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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE218569 | GEO | 2023/07/06

REPOSITORIES: GEO

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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.

2023-07-06 | GSE218568 | GEO

Transcriptome analysis of human reninomas as an approach to understanding juxtaglomerular cell biology

Project description:Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. Although these cells line the media of the glomerular afferent arterioles and share some characteristics with contractile cells, they are filled with lysosome-like organelles where renin is activated and stored for regulated secretion in response to physiological and pathophysiological stimuli. Chronic stimulation of renin release results in a recruitment of new JG cells by the seeming conversion of adjacent smooth muscle cells along the afferent arterioles. Because JG cells rapidly de-differentiate when removed from the kidney, their developmental origin and the mechanism that explains their phenotypic plasticity remain largely unclear. In an effort to overcome this limitation, we have performed RNA expression analysis on four human renin-producing tumors. The most highly expressed genes that were common between the reninomas were subsequently used for in situ hybridization in mouse kidney. Our results add 40 new genes to the list that characterize renin-producing cells and reveal a significant variation in the expression patterns of developing, mature and recruited JG cells.

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Mouse kidney arteriolar smooth muscle cells derived from the renin cell lineage: control vs. forskolin treatment to induce renin expression

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Mouse kidney arteriolar smooth muscle cells derived from the renin cell lineage: control vs. forskolin treatment to induce renin expression

Project description:miRNA profiling of mouse kidney arteriolar smooth muscle cells (aSMCs) of the renin lineage comparing control untreated cells with cells treated with forskolin to induce renin expression. Two condition experiment: control untreated aSMCs vs forskolin treated aSMCs; Biological replicates: control 3, treated 3; independently grown and harvested. One replicate per array.

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Mouse isolated kidney preglomerular arterioles: wild type vs conditional knockout of RBP-J in renin cells

Project description:mRNA profiling of mouse kidney preglomerular arterioles comparing wild type arterioles vs.arterioles from mice having deletion of RBP-J in cells of the renin lineage We used microarrays to detail the global program of gene expression in wild type and RBP-J conditional knockout (RPB-J cKO) kidney arterioles which revealed upregulation of genes that belong to the immune response system.

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2017-02-19 | GSE89811 | GEO

RNA-Seq As4.1 cell line and native renin cells isolated from Ren1c-YFP mice

Project description:RNA-seq was performed to compare the transcriptome of three renin cell types: juxtaglomerular cells, cells isolated from chronically recruited mice and in As4.1 cells

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Proteomic Profiles of Human Arterioles Isolated from Fresh Adipose Tissue or Following Overnight Storage

Project description:Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5µg, making proteomic analysis challenging. In addition, obtaining human arterioles requires manual dissection of unfrozen clinical specimens. This limits its feasibility, especially for powerful multi-center clinical studies in which clinical specimens need to be shipped overnight to a research lab for arteriole isolation. We performed a study to address low input, test overnight tissue storage, and develop a reference human arteriolar proteomic profile. In tandem mass tag proteomics, use of a booster channel consisting of human induced pluripotent stem cells-derived endothelial and vascular smooth muscle cells (1:5 ratio) increased the number of proteins detected in a human arteriole segment with FDR < 0.01 from 1,051 to more than 3,000. The correlation coefficient of proteomic profile was similar between replicate arterioles isolated freshly, following cold storage, or before and after the cold storage (one-way ANOVA, p=0.60). We built a human arteriolar proteomic profile consisting of 3,832 proteins based on the analysis of 12 arteriole samples from three subjects. Of 1,945 BP-relevant proteins that we curated, 476 (12.5%) were detected in the arteriolar proteome, which was a significant overrepresentation (Chi-squared, p<0.05). These findings demonstrate that proteomic analysis is feasible with arterioles isolated from human adipose tissue following cold overnight storage and provide a reference human arteriolar proteome profile highly valuable for studies of arteriole-related traits.

2024-03-21 | PXD044454 | Pride

Synaptic-like transmission between neural axons and arterial smooth muscle cells drives cerebral neurovascular coupling

Project description:Normally functioning brains depend on neurovascular coupling (NVC) and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is specifically conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrated that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cells junction (NsMJ). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscles cells (aSMCs), which expressed many types of neuromediator receptors, including glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission, by aSMC specific knockout of GluN1, diminished the optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs protected the brain atrophy from cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives neurovascular coupling and also open up a new avenue for studying stroke.

2023-10-05 | GSE213026 | GEO

Mus musculus

Project description:Mouse kidney arteriolar smooth muscle cells derived from the renin cell lineage: control vs. forskolin treatment to induce renin expression

| PRJNA145289 | ENA

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