Histone Methylation Regulates Nephron Progenitor Cell Fate in Mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE40742 | GEO | 2013/08/28
SECONDARY ACCESSION(S): PRJNA174807
REPOSITORIES: GEO
Similar Datasets
Project description:We report the use of high-throughput sequencing of histone methylation ChIP to compare the H3K4me3 and H3K27me3 methylation states in sequential mouse nephron progenitor lineages Examination of 2 different histone modifications in 2 cell types.
2013-08-28 | E-GEOD-40742 | biostudies-arrayexpress
Project description:The kidney contains the functional units, the nephrons, surrounded by the renal interstitium. Previously, we discovered that, once Six2-expressing nephron progenitor cells and Foxd1-expressing renal interstitial progenitor cells form at the onset of kidney development, descendant cells from these populations contribute exclusively to the main body of nephrons and renal interstitial tissues, respectively, indicating a lineage boundary between the nephron and renal interstitial compartments. Currently, it is unclear how lineages are regulated during kidney organogenesis. We demonstrate that nephron progenitor cells lacking Pax2 activity failed to differentiate into nephron cells, but can switch fates into renal interstitium cell types. These data suggest that Pax2 function maintains nephron progenitor cells by repressing transdifferentiation into renal interstitial cell states. Thus, the lineage boundary between the nephron and renal interstitial compartments is maintained by the Pax2 activity in nephron progenitor cells during kidney organogenesis.
2017-03-11 | GSE79137 | GEO
Project description:H3K4me3 Mint-ChIP-seq on human H9 derived nephron progenitor cell For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-06-15 | GSE177761 | GEO
Project description:H3K27me3 Mint-ChIP-seq on human H9 derived nephron progenitor cell For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2022-07-22 | GSE208994 | GEO
Project description:Background: Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multi-step process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the nephron exists. Results: Here, we identify LGR6 as a NPC marker, expressed in very early cap mesenchyme, pre-tubular aggregates, renal vesicles and in segments of S-shaped bodies, following the trajectory of MET. By using a lineage tracing approach in embryonic explants in combination with confocal imaging and single-cell RNA sequencing, we provide evidence for the multiple fates of LGR6+ cells during embryonic nephrogenesis. Moreover, by using long-term in vivo lineage tracing, we show that postnatal LGR6+ cells are capable of generating the multiple lineages of the nephrons. Conclusion: Given the profound early mesenchymal expression and MET signature of LGR6+ cells, together with the lineage tracing of mesenchymal LGR6+ cells, we conclude that LGR6+ cells contribute to all nephrogenic segments by undergoing MET. LGR6+ cells can therefore be considered an early committed NPC population during embryonic and postnatal nephrogenesis with potential regenerative capability.
2021-05-25 | GSE164795 | GEO
Project description:Eya1 is a critical regulator for establishing nephron fate and acts upstream of Six2. However, how Eya1-centered network operates remains elusive. Here we identified Eya1's interacting factors via mass-spectrometry and show that Eya1 and Six2 interact with Brg1-based SWI/SNF chromatin-remodeling complex in the kidney. Brg1 specifies the nephron fate and regulates Eya1 expression through binding to multiple cis-regulatory-elements. In the nephron-progenitors, Brg1/Six2 co-occupy cis-regulatory-elements at key loci and Brg1-recruitment to many of these regions is disrupted in the absence of Six2. We demonstrate Six2-dependent Brg1-occupancy to Mycn promoter and two distal enhancers of Pbx1, all of which direct nephron-progenitor-specific expression in response to binding to Six2. RNA-seq analysis reveals that depletion of Brg1 leads to upregulation of genes for podocyte-lineages and aberrant activation of cell-death inducing factors. Together, this study highlights an essential function of the Brg1-BAFs in cooperation with Eya1/Six2 in enhancer-mediated regulation of gene expression in the nephron-progenitors.
2023-10-12 | GSE159483 | GEO
Project description:Regulation of the balance between progenitor self-renewal and differentiation is critical to development. In the mammalian kidney, reciprocal signaling between three lineages (stromal, mesenchymal and ureteric) ensures correct nephron progenitor self-renewal and differentiation. Loss of either the atypical cadherin Fat4 or its ligand Dachsous1 (Dchs1) results in expansion of the mesenchymal nephron progenitor pool, called the condensing mesenchyme (CM). This has been proposed to be due to misregulation of the Hippo kinase pathway transcriptional co-activator YAP. Here, we use tissue-specific deletions to prove that Fat4 acts non-autonomously in the renal stroma to control nephron progenitors. We show that loss of Yap from the CM in a Fat4-null background does not reduce the expanded CM, indicating Fat4 regulates the CM independent of YAP. Analysis of Six2-/-;Fat4-/- double mutants demonstrates that excess progenitors in Fat4 mutants are dependent on Six2, a critical regulator of nephron progenitor self-renewal. Electron microscopy reveals that cell organization is disrupted in Fat4 mutants. Gene expression analysis demonstrates that the expression of Notch and FGF pathway components are altered in Fat4 mutants. Finally, we show that Dchs1, and its paralog Dchs2 function in a partially redundant fashion to regulate the number of nephron progenitors. Our data supports a model in which FAT4 in the stroma binds to DCHS1/2 in the CM to restrict progenitor self-renewal. A total of 3 Fat4-/- mutant embryos and 3 wildtype (Fat4+/+) control embryos were examined. Two kidneys from each embryo was used thereby yielding a total of 6 Fat4-/- mutant kidneys and 6 Fat4+/+ wildype kidneys. All kidneys examined were at E13.5.
2015-08-01 | E-GEOD-70452 | biostudies-arrayexpress
Project description:p53 limits the self-renewing ability of a variety of stem cells. Here, contrary to its classical role in restraining cell proliferation, we demonstrate a divergent function of p53 in maintenance of self-renewal of the nephron progenitor population in the embryonic mouse kidney. p53-null nephron progenitor cells (NPC) exhibit progressive loss of the self-renewing progenitor niche in the cap mesenchyme, identified by Cited1 and Six2 expression, and loss of cap integrity. Nephron endowment is regulated by NPC availability and their differentiation to nephrons. Quantitatively, the Six2p53-/- cap has 30% fewer Six2GFP+ cells. While the apoptotic index is unchanged the proliferation index is significantly lower, in accordance with cell cycle analysis data showing less mutant Six2p53-/-;GFP+ cells in S and G2/M phases in comparison to Six2p53+/+;GFP+ cells. The mutant kidneys also show nephron deficit and decreased Fgf8 expression. To investigate the underlying changes in gene expression in the cap mesenchyme that contribute to the Six2p53-/- phenotype, we utilized RNA-Seq for transcriptome comparison. Top biological processes affected by p53 loss are development and morphogenesis, cell adhesion/migration, cell survival and metabolism. Cells from the mutant CM showed increased cellular ROS levels as well as deregulated expression of energy metabolism and mitochondrial genes suggesting metabolic dysfunction. Adhesion defects are visualized by decreased immunostaining of adhesion marker NCAM, and may possibly contribute to the differentiation defect as well. Altogether our data suggest a novel role for p53 in enabling self-renewal of the NPC and preservation of the progenitor niche, and thus regulating nephron endowment. mRNA profiles of wild-type (WT) and conditional p53 knockout (KO) of Six2+ mouse nephron progenitor cells (NPC) at embryonic day 15.5
2015-02-16 | E-GEOD-56253 | biostudies-arrayexpress
Project description:Purpose: To use single-cell RNA-Seq analysis of nephron progenitors in order to determine transcrptional differences as nephron progenitors age. Methods: Using a combination of FACS sorting and a Fluidigm Single-cell auto-prep system, we generated high-throughput RNA-SEQ data of nephron progenitors during development Results: Single cells transcriptome profiling of nephron progenitors revealed progressive age-dependent changes with heterogeneity increasing in older populations. 96-single cell transcriptomes were determined from nephron progenitors of e14.5, e18.5 and P0 using Cited1GFP transgenic animals
2015-12-23 | E-GEOD-66202 | biostudies-arrayexpress
Project description:Nephron number is a major determinant of long-term renal function. We hypothesized a link between epigenetic regulation and nephron formation. In support of this hypothesis, expression analysis evidenced high levels of DNA methyltransferases Dnmt1 and Dnmt3a in the nephrogenic zone of the developing mouse kidney. Using targeted loss-of-function manipulations in mice, we show that deletion of Dnmt1 in nephron progenitor cells results in a marked hypoplasia and reduction of nephron number at birth. In contrast, deletion of Dnmt3a/3b in nephron progenitor cells or deletion of Dnmt1/3a/3b in differentiated renal cells did not lead to any overt kidney phenotype. Whole mount optical projection tomography and 3D-reconstructions uncovered a significant reduction of stem cell niches and progenitor cells in Dnmt1-deficient mice. Ultimately, RNA sequencing analysis revealed that Dnmt1 controls DNA transcription regulating progenitor renewal, identity and differentiation. In summary, this study establishes DNA methylation as key regulatory event of prenatal renal programming.
2019-11-15 | GSE94089 | GEO