Chromatin and gene-regulatory dynamics of mouse nephron progenitors at single-cell resolution
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PROVIDER: PRJNA750040 | ENA |
REPOSITORIES: ENA
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Project description:Chromatin and gene-regulatory dynamics of mouse nephron progenitors at single-cell resolution [scATAC-Seq]
| PRJNA750047 | ENA
Project description:Background: We reasoned that unraveling the dynamic changes in accessibility of genomic regulatory elements and gene expression at single-cell resolution will inform the basic mechanisms of nephrogenesis. Methods: We performed single-cell ATAC-seq and RNA-seq both individually (Singleomes; Six2GFP cells) and jointly in the same cells (Multiomes; kidneys) to generate integrated chromatin and transcriptional maps in mouse embryonic and neonatal nephron progenitor cells (NPCs). Results: We demonstrate that singleomes and multiomes are comparable in assigning most cell states, identification of new cell type markers, and defining the transcription factors driving cell identity. However, multiomes are more precise in defining the progenitor population. Multiomes identified a “pioneer” bHLH/Fox motif signature in NPCs. Moreover, we identified a subset of Fox factors exhibiting high chromatin activity in podocytes. One of these Fox factors, Foxp1, is important for nephrogenesis. Key nephrogenic factors are distinguished by strong correlation between linked gene-regulatory elements and gene expression. Conclusion: Mapping the regulatory landscape at single-cell resolution informs the regulatory hierarchy of nephrogenesis. Paired single-cell epigenomes and transcriptomes of nephron progenitors should provide a foundation to understand prenatal programming, regeneration following injury, and ex vivo nephrogenesis.
2022-04-01 | GSE199928 | GEO
Project description:Background: Unraveling the dynamic accessibility of regulatory chromatin at single-cell resolution is key to understanding stem/progenitor cell fate choices in health and disease. Nephron progenitor cells (NPCs) are a multipotent population giving rise to all cell types of the nephron, from the glomerular epithelium to the distal tubule. At any given time, the NPC’s choice to self-renew or differentiate and gain a new identity is determined not only by its transcription factor repertoire but also by the genome accessibility of the cognate cis-regulatory elements. Methods: We performed singleome and multiome analysis of chromatin accessibility and gene expression in thousands of embryonic and neonatal NPCs toward defining the regulatory landscape driving fate choices during nephrogenesis. Results: We show that chromatin accessibility recovers the diverse states of NPCs and precursor states of proximal and distal nephron epithelial cells. We define the key cell type-specific transcriptional regulators across pseudotime and NPC age. We find that chromatin accessibility in the podocyte lineage is established early in the trajectory and identify a subset of Forkhead factors exhibiting high chromatin activity in podocyte precursors. We also determined that strong linkages between cis-regulatory elements and expression levels distinguish fate-determining TFs. Conclusions: Single-cell mapping of accessible and active chromatin defines the regulatory landscape of nephrogenesis and provides a foundation for future studies in disease states characterized by abnormal nephrogenesis.
2022-04-01 | GSE180898 | GEO
Project description:Single-cell chromatin and gene-regulatory dynamics of mouse nephron progenitors [ChIP-seq]
| PRJNA822124 | ENA
Project description:Chromatin and gene-regulatory dynamics of mouse nephron progenitors at single-cell resolution [Single cell Multiome ATAC + Gene Expression]
| PRJNA750048 | ENA
Project description:Background: Unraveling the dynamic accessibility of regulatory chromatin at single-cell resolution is key to understanding stem/progenitor cell fate choices in health and disease. Nephron progenitor cells (NPCs) are a multipotent population giving rise to all cell types of the nephron, from the glomerular epithelium to the distal tubule. At any given time, the NPC’s choice to self-renew or differentiate and gain a new identity is determined not only by its transcription factor repertoire but also by the genome accessibility of the cognate cis-regulatory elements. Methods: We performed singleome and multiome analysis of chromatin accessibility and gene expression in thousands of embryonic and neonatal NPCs toward defining the regulatory landscape driving fate choices during nephrogenesis. Results: We show that chromatin accessibility recovers the diverse states of NPCs and precursor states of proximal and distal nephron epithelial cells. We define the key cell type-specific transcriptional regulators across pseudotime and NPC age. We find that chromatin accessibility in the podocyte lineage is established early in the trajectory and identify a subset of Forkhead factors exhibiting high chromatin activity in podocyte precursors. We also determined that strong linkages between cis-regulatory elements and expression levels distinguish fate-determining TFs. Conclusions: Single-cell mapping of accessible and active chromatin defines the regulatory landscape of nephrogenesis and provides a foundation for future studies in disease states characterized by abnormal nephrogenesis.
2022-04-01 | GSE180900 | GEO
Project description:During mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling. Nephron progenitors were FACS-isolated from BAC transgenic Six2GFPcre-positive embryonic kidneys at E16.5. Cells were aggregated by centrifugation at 850g for 5min and incubated in 10%FBS/DMEM containing either 4uM BIO or the equal volume of DMSO for 24hrs or 48hrs.
2012-09-11 | E-GEOD-39583 | biostudies-arrayexpress
Project description:Self-renewing undifferentiated nephron progenitors express Six2, a transcription factor that is required for their maintenance as undifferentiated progenitors. Differentiation of nephron progenitors is triggered by Wnt/b-catenin signaling. In order to understand how Six2 and Wnt signaling counteract each other, we performed ChIP-seq of Six2 and b-catenin in mesenchymal nephron progenitor cells. Nephron progenitors were FACS-isolated from BAC transgenic Six2GFPcre-positive embryonic kidneys at E16.5. For Six2 ChIP, freshly FACS isolated Six2+ cells were used. For b-catenin ChIP, FACS isolated Six2+ cells were aggregated by centrifugation at 850g for 5min and incubated in 10%FBS/DMEM containing 4uM BIO for 24hrs.
2012-09-11 | E-GEOD-39837 | biostudies-arrayexpress
Project description:Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, the progenitors in mice terminally differentiate shortly after birth. We defined culture conditions to selectively propagated nephron progenitors in vitro in an undifferentiated state. To understand how expression profiles of Six2+ cells changed during culture in vitro compared with in vivo, we performed microarray analysis of Six2+ cells at E11.5 (starting material) and P0 (experiencing 8 days in vivo), and cultured Six2+ cells at E11.5 for 8 days or 19 days. Microarray analysis were performed with isolated Six2-positive nephron progenitors from transgenic mice embryo at E11.5 or P0, and cultured E11.5 Six2+ cells for 8 or 19 days in conditioned media. P0 non-progenitors represent Six2-GFP-negative cells at P0.
2016-04-14 | E-GEOD-79024 | biostudies-arrayexpress
Project description:During mammalian kidney development, mesenchymal nephron progenitors (cap mesenchyme) differentiate into the epithelial cells that go on to form the nephron. Although differentiation of nephron progenitors is triggered by activation of Wnt/b-catenin signaling, constitutive activation of Wnt/b-catenin signaling blocks epithelialization of nephron progenitors. Full epithelialization of nephron progenitors requires transient activation of Wnt/b-catenin signaling. We performed transcriptional profiling of nephron progenitors responding to constitutive or transient activation of Wnt/b-catenin signaling.
2012-09-11 | GSE39583 | GEO