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Genomic landscape of the developing kidney upon conditional and time-dependent knockout of Wt1

ABSTRACT: We are characterizing global expression in the whole kidney at developmental stage E18.5, where we have used three Cre strains that result in knock out Wt1 in different cell types during renal development. Here the purpose is to identify the developmental stage at which the loss of Wt1 impacts kidney development, specifically in the context of a degree of disruption capable of ending in pediatric kidney cancers.

ORGANISM(S): Mus musculus

PROVIDER: GSE70892 | GEO | 2015/07/27

SECONDARY ACCESSION(S): PRJNA290376

REPOSITORIES: GEO

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Genomic landscape of the developing kidney upon conditional and time-dependent knockout of Wt1

Project description:We are characterizing global expression in the whole kidney at developmental stage E18.5, where we have used three Cre strains that result in knock out Wt1 in different cell types during renal development. Here the purpose is to identify the developmental stage at which the loss of Wt1 impacts kidney development, specifically in the context of a degree of disruption capable of ending in pediatric kidney cancers. Total RNA was isolated from whole kidneys of E18.5 mouse embryos following a variety of conditional knockouts of Wt1, plus appropriate control animals.

2015-07-27 | E-GEOD-70892 | biostudies-arrayexpress

Genome wide WT1 binding sites in developing mouse kidneys

Project description:We report the the identification of chrosomal regions bound by the Wilms' tumor suppressor gene WT1 during embryonic mouse kidney development. Two indepednent ChIP-Seq experiments on microdissected E18.5 developing mouse kidneys were carried out using either WT1-specific or IgG-antibodies as a negative control.

2014-06-15 | E-GEOD-58179 | biostudies-arrayexpress

Genome wide WT1 binding sites in developing mouse kidneys

Project description:We report the the identification of chrosomal regions bound by the Wilms' tumor suppressor gene WT1 during embryonic mouse kidney development.

2014-06-15 | GSE58179 | GEO

Chromatin immunoprecipitation of mouse embryonic kidney tissue and anti-WT1 antibody

Project description:ChIP-chip study using embryonic E18.5 mouse kidney tissue and anti-WT1 antibody (Santa Cruz C19 and N180) performed in three technical replicates. ChIP DNA was not PCR amplified prior to hybridization to Agilent 244K mouse promoter arrays, to avoid potential PCR amplification bias.

2010-06-09 | E-TABM-872 | biostudies-arrayexpress

Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice

Project description:BACKGROUND: Lim1 is a homeobox gene that is essential for nephrogenesis. During metanephric kidney development, Lim1 is expressed in the nephric duct, ureteric buds, and the induced metanephric mesenchyme. Conditional ablation of Lim1 in the metanephric mesenchyme blocks the formation of nephrons at the nephric vesicle stage, leading to the production of small, non-functional kidneys that lack nephrons. METHODS: In the present study, we used Affymetrix probe arrays to screen for nephron-specific genes by comparing the expression profiles of control and Lim1 conditional mutant kidneys. Kidneys from two developmental stages, embryonic day 14.5 (E14.5) and 18.5 (E18.5), were examined. RESULTS: Comparison of E18.5 kidney expression profiles generated a list of 465 nephron-specific gene candidates that showed a more than 2-fold increase in their expression level in control kidney versus the Lim1 conditional mutant kidney. Computational analysis confirmed that this screen enriched for kidney-specific genes. Furthermore, at least twenty-eight of the top fifty (56%) candidates (or their vertebrate orthologs) were previously reported to have a nephron-specific expression pattern. Our analysis of E14.5 expression data yielded 41 candidate genes that are up-regulated in the control kidneys compared to the conditional mutants. Three of them are related to the Notch signaling pathway that is known to be important in cell fate determination and nephron patterning. CONCLUSIONS: Therefore, we demonstrate that Lim1 conditional mutant kidneys serve as a novel tissue source for comprehensive expression studies and provide a means to identify nephron-specific genes. Keywords: tissue specificity, time course, development, kidney, metanephric mesenchyme, nephron, Lim1, knockout mice, conditional knockout

2006-02-13 | GSE4230 | GEO

N-degradomic analysis of proteolytic processing in WT1 heterozygous mice

Project description:N-degradomic analysis of proteolytic processing in WT1 heterozygous mice, suffering from genetically induced chronic kidney injury, compared to wild type

2021-02-15 | PXD023292 | Pride

Exon Array analysis of WT1(+KTS) mutant mice

Project description:This exon array analysis was performed on mice carrying splice specific mutations at the end of exon9 of the Wilms tumor supressor gene that interfere with the production of WT1(+KTS) isoforms (Hammes et al., 2001; Cell 106:309) 4 wildtype and 4 wt1(+KTS) mutant E18.5 mouse embryos were transcardially perfused with magnetic beads, glomeruli isolated and RNA extracted and analyzed for differential expression on Affymetrix Exon Arrays

2015-03-27 | E-GEOD-67313 | biostudies-arrayexpress

WT1+ parietal epithelial progenitor cells are essential for renal proximal tubule repair and regeneration

Project description:Purpose: We have found that WT1+ parietal epithelial progenitor cells contribute to renal proximal tubule repair and regeneration by cell lineage tracing and direct differentiation analysis, but the transcription profile of these WT1+ PECs is largely unkown. Here, we aimed to unveil the transcriptional features of WT1+ PECs through single-cell RNA sequencing (scRNA-seq). Methods: Single cell suspension was prepared from kidney cortex of WT1CreERT2; Rosa26-tdTfl/+ mice that underwent sham or ischemic reperfusion injury (IRI) 24h .TdT+ cells were enriched by fluorescence activated cell sorter (FACS) and further analyzed with BD Rhapsody platform. Results: After quality control and cell filtering, 26,759 cells were informative (Dataset S1) and divided into 10 clusters using Harmony algorithm to reduce batch effects. GO analysis and QuSAGE heatmap suggested that WT1+ PECs might promote kidney regeneration after AKI through TGF-β and Notch signaling pathway. Marker gene expression analysis showed that WT1+ PECs shared the characteristics of STCs. Pseudotemporal analysis indicated that that WT1+ PECs developed to PTECs through STCs intermediate stage. Conclusions: scRNA-seq indicated that the rare, quiescent PECs supplied PTECs through STCs intermediate stage after severe ischemic injury, and this process most likely was regulated through TGF-β and Notch signaling pathway.

2023-03-22 | GSE184601 | GEO

Gene expression profiling of Wt1 mutant renal anlagen

Project description:Wt1 is required for renal development and homozyogus knockout mice show renal agenesis caused by apoptosis of the metanepric mesnchyme. To identify genes regulated by WT1, we performed comparative gene expression profiling on kidney rudmients of Wt1 heterozygous and homozygous mutant E10.25 embryos.

2014-06-01 | GSE58073 | GEO

FOXC2 and WT1 regulate transcriptional reprogramming during the podocyte response to injury

Project description:In the context of human disease, the mechanisms whereby transcription factors reprogram gene expression in reparative responses to injury are not well understood. We have studied the mechanisms of transcriptional reprogramming in disease using murine kidney podocytes as a model for tissue injury. Podocytes are a crucial component of glomeruli, the filtration units of each nephron. Podocyte injury is the initial event in many processes that lead to End Stage Kidney Disease. FOXC2 is a transcription factor known to regulate gene expression in podocytes. FOXC2 and WT1 are both required for podocyte differentiation. Using murine models and human kidney organoids, we investigated FOXC2-mediated transcriptional reprogramming during the course of podocyte injury. Correlating FOXC2 and WT1 ChIP-seq analyses demonstrated that they co-bind many genes expressed in podocytes. Reprogramming the transcriptome involved highly dynamic changes in the binding of FOXC2 and WT1 to target genes during a reparative injury response.

2023-11-01 | GSE213174 | GEO

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