Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular determinants of nephron vascular specialization in the kidney

ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE137786 | GEO | 2019/09/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury

Project description:Background: The kidney glomerulus is a specialized capillary bed that is involved in urine production and blood pressure control. Glomerular injury is a major cause of chronic kidney disease, a widespread epidemic without therapeutic options. Single-cell transcriptomics have radically improved our ability to characterize complex organs, such as the kidney. Cells of the glomerulus, however, have been largely underrepresented in previous single cell kidney studies due to their paucity and intractability. Methods: We used single-cell RNA sequencing to comprehensively characterize the different types of cells in the glomerulus from healthy mice and from four different disease models (nephrotoxic serum nephritis, diabetes, doxorubicin toxicity, CD2AP deficiency). Results: All cell types in the glomerulus were identified using unsupervised clustering analysis. We identified novel marker genes and gene signatures of mesangial cells, vascular smooth muscle cells of the afferent and efferent arteriole, parietal epithelial cells, and three different types of endothelial cells. Analysis of the disease models revealed cell type-specific and injury type-specific responses in the glomerulus, including acute activation of the Hippo pathway in podocytes after nephrotoxic immune injury. Conclusions: We have generated a comprehensive high-resolution single-cell transcriptomic profile of the kidney glomerulus from healthy and injured mice. The dataset provides a useful resource for identifying novel disease-related genes and pathways.

2020-07-13 | GSE146912 | GEO

Role of Gata5 in vascular endothelial cells

Project description:Despite its high prevalence and economic burden, the etiology of human hypertension remains incompletely understood. Here we identify the transcription factor Gata5, as a new gene involved in regulation of blood pressure (BP). GATA5 is expressed in microvascular endothelial cells (mEC) and its genetic inactivation in mice leads to hypertension, vascular endothelial dysfunction and renal inflammation. Aged Gata5-Null mice develop salt-sensitivity and target-organ damage reminiscent of the progression of human hypertension. Endothelial-specific inactivation of Gata5 increases BP and leads to vascular endothelial dysfunction, confirming the endothelial component of Gata5 inactivation-related hypertension. To directly assess the effect of loss of GATA5 on endothelial cells, we generated a stable GATA5 knockdown cell line (HDMEC-Gata5KO) by infecting human dermal microvascular endothelial cells with a lentiviral vector containing an anti-Gata5 shRNA followed by a transcriptomic analysis. The control cells were infected with a lentivirus containing an empty vector pLKO2.

2015-10-01 | GSE71838 | GEO

Cellular recruitment by podocyte-derived pro-migratory factors in assembly of the human renal filter

Project description:Analysis of monogenic kidney disease-causing genes, and secondary pathology resulting from systemic diseases including diabetes and hypertension, highlight the importance of the kidney’s filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we employed single-nucleus droplet-based sequencing to capture single nuclei from the human fetal kidney. This enabled the identification of distinct cell types of the nephron (podocytes), interstitial (mesangial cells) and vascular (glomerulus) lineages that together generate the renal corpuscles. Computational trajectory analysis identified transient gene expression in the development of these cell types, predicting early precursors or mature podocytes express FBLN2, BMP4 or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types.

2019-10-03 | GSE114569 | GEO

Homo sapiens

Project description:Role of Gata5 in vascular endothelial cells

| PRJNA292301 | ENA

Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes

Project description:Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), were missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we used Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis revealed genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells (MDCs). Importantly, we detected heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observed remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.

2020-11-21 | GSE160048 | GEO

Uncovering the epigenomic determinants of kidney vascular development [scRNA-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 | GSE218569 | GEO

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

2023-07-06 | GSE218568 | GEO

Netrin-1 directs vascular patterning and maturity in the developing kidney

Project description:The kidneys intricate vascular system supports body fluid and organ homeostasis. However, little is known about how vascular architecture is established during kidney development. More specifically, how signals from the kidney influence vessel maturity and patterning remains poorly understood. Netrin-1 (Ntn1) is a secreted ligand critical for vessel and neuronal guidance. Here, we demonstrate that Ntn1 is expressed by Foxd1+ stromal progenitors in the developing kidney and conditional deletion (Foxd1GC/+;Ntn1fl/fl) results in hypoplastic kidneys with extended nephrogenesis. Wholemount 3D analyses additionally revealed the loss of a predictable vascular pattern in Foxd1GC/+;Ntn1fl/fl kidneys. As vascular patterning has been linked to vessel maturity, we investigated arterialization. Quantification of the CD31+ endothelium at E15.5 revealed no differences in metrics such as the number of branches or branch points, whereas the arterial vascular smooth muscle metrics were significantly reduced at both E15.5 and P0. In support of our observed phenotypes, whole kidney RNA-seq revealed disruptions to genes and programs associated with stromal cells, vasculature, and differentiating nephrons. Together, our findings highlight the significance of netrin-1 to proper vascularization and kidney development.

2023-10-19 | GSE245506 | GEO

Effect of Maternal Separation (MatSep) on renal vasculature isolated from male neonates (Postnatal day 10) and adult (Postnatal day 180)

Project description:Optimal Ang II levels during postnatal life are required for a normal maturation of the rat kidney. This study investigated both short- and long-term effect of MatSep on: 1) the status of intrarenal renin-angiotensin system components, 2) the isolated renal vasculature genome-wide gene expression trajectory from neonatal to adult life, and 3) the renal vascular architecture and function. In this dataset, gene expression changes by MatSep at P10 in renal vasculature isolated from neonates, modulate extracellular structure organization, vasculature development, inflammation and angiogenesis. The long -term effects of MatSep on renal vasculature gene expression is assessed at P180, which reveal clusters of genes with short, long, and downstream changes in expression.

2020-08-11 | GSE151402 | GEO

Examining the immediate early targets of Gata4 and Gata5.

Project description:Gata factors are amongst the genes expressed early on in the process of cardiogenesis. We used microarrays to examine the immediate early targets of Gata4 and Gata5 in the Xenopus leavis animal cap cardiogenesis model. We hope to use these data to examine the roles of Gata4 and Gata5 in cardiogenesis and also to begin to dissect out the common and distinct targets of Gata4 and Gata5. Keywords: genetic modification, gene overexpresison.

2008-07-15 | GSE8496 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data