Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Defects in nephrogenesis result in an expansion of the Foxd1+ stromal progenitor population

ABSTRACT: Reciprocal signaling interactions coordinate multiple aspects of kidney development. While signals from the stroma have been shown to regulate nephron progenitor cell (NPC) differentiation, much less is known about regulation of the stromal progenitor population. We sought to further examine how defects in the nephron lineage may non-autonomously affect stromal development. To aid in this analysis, we generated single nuclei RNA-seq using 10x genomics from paired E15.5 control kidneys (cre-negative and Six2creTGC) to identify additional markers of the Foxd1+ stromal progenitor population at this timepoint, and validated the expression of early B cell factor 3 (Ebf3), aldehyde oxidase 3 (Aox3), fibroblast activation protein (Fap), insulin growth factor 1 (Igf1), and glutamate ionotropic receptor AMPA type subunit 1 (Gria1) in control and mutant kidneys.

ORGANISM(S): Mus musculus

PROVIDER: GSE289696 | GEO | 2025/02/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression comparison of E14.5 Foxd1 null and wild type kidneys

Project description:Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. Foxd1 is required during kidney development and its inactivation results in failure of nephron progenitor cell differentiation. Foxd1 is expressed in interstitial cells adjacent to nephron progenitor cells, suggesting an essential role for the progenitor cell niche in nephrogenesis. To better understand how cortical interstitial cells in general, and FOXD1 in particular, influence the progenitor cell niche, we examined the differentiation states of two progenitor cell subtypes in Foxd1-/- tissue. We found that while nephron progenitor cells are retained in a primitive CITED1-expressing compartment, cortical interstitial cells prematurely differentiate. To identify pathways regulated by FOXD1, we used microarray analysis and screened for target genes by comparison of Foxd1 null and wild type tissues. We chose the E14.5 timepoint because at this stage nephron differentiation is present in wild type kidneys but absent from Foxd1 null kidneys. We examined genes that were upregulated or downregulated in the Foxd1 null compared to wild type. Embryonic kidneys were harvested from Foxd1-/- and wild type littermates from three E14.5 litters. Three biological replicates were generated per genotype, each containing two non-littermate kidney pairs. Sex of embryos was not determined.

2013-11-14 | E-GEOD-52354 | biostudies-arrayexpress

Gene expression comparison of E14.5 Foxd1 null and wild type kidneys

2013-11-14 | GSE52354 | GEO

Lgr5+ve stem cells in nephrogenesis

Project description:Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Validated markers of these early stem/progenitor populations are essential for deciphering their in vivo function and for evaluating their clinical potential for treating adult kidney disease. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5+ve cells via in vivo lineage tracing. The appearance and localization of Lgr5+ve cells coincided with that of the S-shaped body around E14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until P7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a novel progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Metanephric kidneys of timed pregnancies of ~14 days of gestation were harvested and cultured for ~10 days. Lgr5-EGFP-Ires-CreERT2-positive embryonic kidneys were identified by fluorescence microscopy and enzymatically digested to a single cell solution. GFPhi and GFPneg cells were sorted by flow cytometry (MoFlo; Dako). RNA, isolated using RNeasy (Qiagen), was analyzed using the Affymetrix platform.

2012-09-04 | E-GEOD-39881 | biostudies-arrayexpress

Gain-of-function ENL YEATS domain mutations impede nephrogenesis through gene expression control [RNA-seq]

Project description:Hotspot gain-of-function mutations in the YEATS domain of the histone reader protein ENL have been identified in Wilms’ tumor. To investigate the pathogenic role of these cancer-associated ENL mutations in kidney development and tumorigenesis in vivo, we generated conditional knock-in mouse models mimicking patient-derived ENL YEATS mutations. Mice with heterozygous expression of ENLT mutants in either Six2+ nephrogenic or Foxd1+ stromal lineage exhibit severe yet distinct defects in kidney development, both resulting in neonatal lethality. The Six2-ENLT mutant kidney rudiments display compromised cap mesenchyme, scant proximal tubules and cystic glomeruli, indicative of premature commitment and differentiation blockade during nephrogenesis. Bulk and spatial transcriptomic analyses uncover aberrant activation of Hox genes and genes involved in cell fate commitment, especially the Wnt signaling pathway, in ENLT mutant-expressing nephrogenic cells. In contrast, the Foxd1-ENLT mutant kidneys exhibit expansion in renal capsule and cap mesenchyme, accompanied with dysregulation of stromal genes involved in nephrogenesis and stroma-nephron crosstalk. Collectively, our study sheds lights on how ENL YEATS domain mutations impede nephrogenesis through different pathways in nephrogenic and stromal lineages, paving the way for further investigations into their roles in tumorigenesis.

2025-02-20 | GSE266256 | GEO

Gain-of-function ENL YEATS domain mutations impede nephrogenesis through gene expression control [Spatial Transcriptomics]

2025-02-20 | GSE283433 | GEO

mRNA-Seq profiling SIX2+ and Foxd1+ cells in mouse embryonic and SIX2+ and SIX2-/MEIS1+ cells human fetal kidney

Project description:To characterize the molecular features of human and mouse nephron progenitors and stromal cells we performed intracellular labeling for SIX2 and/or MEIS1 antibodies, FACS, and RNA-seq. Mouse interstitial progenitors were isolated by Foxd1-Tdt transgenic line, FACS, and RNA-seq

2018-02-14 | GSE102230 | GEO

Defects in nephrogenesis result in an expansion of the Foxd1+ stromal progenitor population

Project description:Defects in nephrogenesis result in an expansion of the Foxd1+ stromal progenitor population

| PRJNA1224207 | ENA

Gene expression profiling of E18.5 FoxD1 Cre;Dicer and control embryonic kidneys

Project description:The aim of this study is to address the functional role of miRNAs in the FoxD1+ renal stroma progenitors and derivatives during embryonic kidney development. To achieve this, we generated transgenic mice that lack miRNAs in the renal stroma lineage (FoxD1 Cre;Dicer), and performed a microarray analysis on E18.5 whole kidneys to determine the transcriptional changes. 3 litters of E18.5 FoxD1 Cre;Dicer and control littermate kidneys were used for the microarray analysis. Each litter consists of kidneys pooled from 2 embryos per genotype for the RNA extraction.

2015-11-04 | E-GEOD-64441 | biostudies-arrayexpress

Gene expression profiling of E18.5 FoxD1 Cre;Dicer and control embryonic kidneys

2015-11-04 | GSE64441 | GEO

Gene expression profiling of E15.5 FoxD1 Cre;Dicer and control embryonic kidneys

2015-11-04 | GSE64440 | GEO