Genome-wide map of open chromatin, trancription factor occupancy, chromatin marks and gene expression profiles in mouse nephron progenitor cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE131119 | GEO | 2021/01/07
REPOSITORIES: GEO
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Project description:Genome-wide map of open chromatin, trancription factor occupancy, chromatin marks and gene expression profiles in mouse nephron progenitor cells
| PRJNA542676 | ENA
Project description:BackgroundNephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multistep 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.ResultsHere, 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.ConclusionsGiven 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.
| S-EPMC8597161 | biostudies-literature
Project description:During embryonic kidney development, nephron progenitor cells (NPCs) self-renew and differentiate into all cells in mature nephrons. The Wnt signaling components Wnt9b and β-catenin are required for both NPC self-renewal and differentiation. A low level of Wnt/β-catenin are associated with NPC self-renewal while a high level with differentiation. To investigate the transcriptional mechanisms behind Wnt/β-catenin-driven regulation of NPCs states, we modeled NPC self-renewal and differentiation in vitro with NPEM (Brown et al., 2015) supplemented with low (1.25 μM) or high (5 μM) concentration of CHIR22091 (CHIR), a small molecule GSK3β inhibitor that stabilizes β-catenin. To investigate change of NPC chromatin landscape under influence of CHIR treatment, here we generated ATAC-Seq data from primary NPC, as well as NPC cultured in low and high CHIR concentration.
2021-01-07 | GSE131116 | GEO
Project description:To delineate the epigenomic profile of the Six2+ mouse nephron progenitor cells, we mapped open chromatin using ATAC-Seq in Six2+ cells from E16.5 mouse kidneys.
2018-01-18 | GSE108424 | GEO
Project description:Genome-wide map of open chromatin in mouse nephron progenitor cells
| PRJNA542683 | ENA
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:LGR6 marks nephron progenitor cells
| PRJNA691957 | ENA
Project description:Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. These maps show that TF occupancy is dynamic between developmental stages and that multiple TFs often collaboratively occupy the same chromatin region through indirect cooperativity. Multi-TF regions exhibit features of functional regulatory elements, including evolutionary conservation, chromatin accessibility, and activity in transcriptional enhancer assays. H3K27ac, a feature of many enhancers, incompletely overlaps multi-TF regions, and multi-TF regions lacking H3K27ac retain conservation and enhancer activity. TEAD1 is a core component of the cardiac transcriptional network, co-occupying cardiac regulatory regions and controlling cardiomyocyte-specific gene functions. Our study provides a resource for deciphering the cardiac transcriptional regulatory network and gaining insights into the molecular mechanisms governing heart development.
| S-EPMC6817842 | biostudies-other
Project description:Mapping open chromatin in mouse nephron progenitor cells
| PRJNA427367 | ENA
Project description:During embryonic kidney development, nephron progenitor cells (NPCs) self-renew and differentiate into all cells in mature nephrons. The Wnt signaling components Wnt9b and β-catenin are required for both NPC self-renewal and differentiation. A low level of Wnt/β-catenin are associated with NPC self-renewal while a high level with differentiation. To investigate the transcriptional mechanisms behind Wnt/β-catenin-driven regulation of NPCs states, we modeled NPC self-renewal and differentiation in vitro with NPEM (Brown et al., 2015) supplemented with low (1.25 μM) or high (5 μM) concentration of CHIR22091 (CHIR), a small molecule GSK3β inhibitor that stabilizes β-catenin. We have found the Tcf/Lef family repressors Tcf7l1 and Tcf7l2 are enriched in low CHIR condition, while the activators Tcf7 and Lef1 in high CHIR condition, correlating with the NPC differentiation program transiting from being repressed to activated. To identify direct transcriptional targets of Tcf/Lef factors and β-catenin, here we generated ChIP-Seq data from primary NPC, as well as NPC cultured in low and high CHIR concentration.
2021-01-07 | GSE131117 | GEO