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Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules

ABSTRACT: Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules

PROVIDER: PRJNA1271983 | ENA |

REPOSITORIES: ENA

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Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules

Project description:The organizational principles of nephronal segments are based on anatomical and physiological attributes that are linked to the homeostatic functions of the kidney. Recent molecular approaches have uncovered layers of deeper signatures and states in tubular cells that arise at various timepoints on the disease trajectory. Here, we introduce an analytical pipeline of multiplexed spatial protein imaging integrated with RNA expression to characterize proximal tubular subpopulations and neighborhoods in human kidney tissue. We demonstrate that, in reference tissue, a large proportion of S1 proximal tubular epithelial cells express THY1, a mesenchymal stromal and stem cell marker that regulates differentiation. Kidney disease is associated with loss of THY1 and transition towards expression of PROM1, another stem cell marker recently linked to failed repair. Our data support a model in which the interplay between THY1 and PROM1 expression in proximal tubules associates with their regenerative potential and marks the timeline of disease progression.

2025-07-20 | GSE298953 | GEO

Gene expression profiles in isolated proximal tubules and whole kidneys of rats after cisplatin-administration

Project description:To clarify the effects of cisplatin (cis-diamminedichloroplatinum II, CDDP) on the gene expression profiles in renal proximal tubules, microarray analyses were carried out using total RNA samples isolated from microdissected proximal tubules and whole kidneys. The molecular events underlying acute kidney injury (AKI) in the proximal tubules of rats with cisplatin-induced nephrotoxicity were successfully clarified with 17,000 transcripts. Renal proximal tubules were isolated under microscopy, and transcriptome data were collected with Rat Genome Survey MicroarrayÂ® (Applied Biosystems)

2013-12-24 | E-GEOD-37133 | biostudies-arrayexpress

Expression data from 20-week-old mice proximal tubules

Project description:dB/dB mice develop different kidney pathologies resulting from high body weight. We seek to better understand the mechanisms of this kidney damage in proximal tubules. We isolated RNA from proximal tubules of different groups of mice, and we seek to understand how the anti-oxidant enzyme catalase may regulate kidney damage in this model.

2009-12-24 | GSE19640 | GEO

Transcription profiling of mouse Clcn5 knockout in proximal tubules of the kidney

Project description:Dent disease has multiple defects attributed to proximal tubule malfunction including low molecular weight proteinuria, aminoaciduria, phosphaturia and glycosuria. In order to understand the changes in kidney function of the Clc5 transporter gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal tubules of mouse kidneys. Overall 720 genes are expressed differentially in the proximal tubules of the Dent Clcn5 knockout mouse model compared to those of control wild type mice. The fingerprint of these gene changes may help us to understand the phenotype of Dent disease. Experiment Overall Design: Renal proximal tubules were dissected from wild type and Clcn5 knockout mice. Mice were anesthetized with halothane, the abdominal aorta of each animal was accessed and the left kidney was perfused with an ice-cold salt. Proximal tubule dissection was performed in an ice-cold salt solution. After dissection of approximately 80-100 segments of 2 mm in length per kidney, the RNA for 3-4 mice was combined to have enough RNA per chip. Experiment Overall Design: 3 microarrays each of wild type and knockout mouse proximal tubule were processed

2008-06-11 | E-GEOD-10162 | biostudies-arrayexpress

Single nucleus RNA sequencing of mosiac Pax2 and Pax8 mutant proximal tubules

Project description:Pax2 and Pax8 are homologous transcription factors required for kidney development and medullary urine concentration. However, their function in proximal tubule homeostasis and response to acute kidney injury is unknown. Mice with proximal tubules consisting of a mosaic of wild-type and Pax2/8 mutant proximal tubules cells were generated. Gene expression of mutant and wild-type proximal tubule cells was compared under homeostatic conditions using single-nucleus RNA sequencing.

2024-11-15 | GSE278289 | GEO

Gene expression profiles in isolated proximal tubules and whole kidneys of rats after cisplatin-administration

2013-12-24 | GSE37133 | GEO

Transcriptional Adaptation to Clcn5 Knockout in Proximal Tubules of the Mouse Kidney

2008-04-03 | GSE10162 | GEO

Expression changes in mouse proximal tubules during primary culture

Project description:Primary cultures of proximal tubule cells are widely used to model the behavior of kidney epithelial cells in vitro. De-differentiation of primary cells upon culture has been observed and appreciated for decades, yet the mechanisms driving this phenomenon remain poorly understood. The goal of this experiment was to quantitatively measure the changes in expression of purified proximal tubules as they enter primary culture.

2024-09-17 | GSE273058 | GEO

Expression changes in mouse proximal tubules during primary culture

Project description:Expression changes in mouse proximal tubules during primary culture

| PRJNA1139850 | ENA

Targeting kidney proximal tubules by protein nanocages via glomerular filtration

Project description:Nature exploits cage-like proteins for a variety of biological purposes from molecular packaging and cargo delivery to catalysis. These cage-like proteins are of immense importance in nanomedicine due to their propensity to self-assemble from simple identical building blocks to highly-ordered architecture and the design flexibility afforded by protein engineering. However, delivery of protein nanocages to the renal tubules remains a major challenge because of the glomerular filtration barrier, which effectively excludes conventional size nanocages. Here we show that DNA-binding Protein from Starved cells (Dps)—the extremely small archaeal antioxidant nanocage—is able to cross the glomerular filtration barrier and is endocytosed by the renal proximal tubules. Using a model of endotoxemia, we present an example of the way in which proximal tubule-selective Dps nanocage can limit the degree of endotoxin-induced kidney injury. This was accomplished by amplifying the endogenous antioxidant property of Dps with addition of a dinuclear manganese cluster. Dps is the first-in-class, protein cage nanoparticle that can be targeted to renal proximal tubules through glomerular filtration. In addition to its therapeutic potential, chemical and genetic engineering of Dps will offer a novel nanoplatform to advance our understanding of the physiology and pathophysiology of glomerular filtration and tubular endocytosis.

2019-05-30 | GSE131922 | GEO

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