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PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors [RNA-seq]

ABSTRACT: In order to understand the epigenetic mechanisms directing development and differentiation of SOX9+ lung epithelial progenitor cells (EPCs), paired RNA-Seq and ATAC-Seq was performed on SOX9+ EPCs sorted using flow cytometry from a Sox9-GFP reporter mouse.

ORGANISM(S): Mus musculus

PROVIDER: GSE188230 | GEO | 2022/08/25

REPOSITORIES: GEO

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PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors [ATAC-seq]

Project description:In order to understand the epigenetic mechanisms directing development and differentiation of SOX9+ lung epithelial progenitor cells (EPCs), paired RNA-Seq and ATAC-Seq was performed on SOX9+ EPCs sorted using flow cytometry from a Sox9-GFP reporter mouse.

2022-08-25 | GSE188237 | GEO

PI3K signaling specifies proximal-distal fate by driving a developmental gene regulatory network in SOX9+ mouse lung progenitors.

Project description:The tips of the developing respiratory buds are home to important progenitor cells marked by the expression of SOX9 and ID2. Early in embryonic development (prior to E13.5), SOX9+progenitors are multipotent, generating both airway and alveolar epithelium, but are selective progenitors of alveolar epithelial cells later in development. Transcription factors, including Sox9, Etv5, Irx, Mycn, and Foxp1/2 interact in complex gene regulatory networks to control proliferation and differentiation of SOX9+progenitors. Molecular mechanisms by which these transcription factors and other signaling pathways control chromatin state to establish and maintain cell-type identity are not well-defined. Herein, we analyze paired gene expression (RNA-Seq) and chromatin accessibility (ATAC-Seq) data from SOX9+ epithelial progenitor cells (EPCs) during embryonic development in Mus musculus. Widespread changes in chromatin accessibility were observed between E11.5 and E16.5, particularly at distal cis-regulatory elements (e.g. enhancers). Gene regulatory network (GRN) inference identified a common SOX9+ progenitor GRN, implicating phosphoinositide 3-kinase (PI3K) signaling in the developmental regulation of SOX9+ progenitor cells. Consistent with this model, conditional ablation of PI3K signaling in the developing lung epithelium in mouse resulted in an expansion of the SOX9+ EPC population and impaired airway epithelial cell differentiation. These data demonstrate that PI3K signaling is required for epithelial patterning during lung organogenesis, and emphasize the combinatorial power of paired RNA and ATAC seq in defining regulatory networks in development.

| S-EPMC9427112 | biostudies-literature

PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-25 | GSE188239 | GEO

PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors

Project description:PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors

| PRJNA777958 | ENA

PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors [RNA-seq]

Project description:PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors [RNA-seq]

| PRJNA777948 | ENA

PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors [ATAC-seq]

Project description:PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in SOX9+ Lung Progenitors [ATAC-seq]

| PRJNA777957 | ENA

SOX9 targets in hESC-derived pancreatic progenitors

Project description:Our lab identified Sox9 as a specific marker and maintenance factor of mouse pancreatic progenitors (Seymour et al., PNAS, 2007). Here was wanted to identify direct targets of Sox9 in pancreatic progenitors. However, due to the limited number of pancreatic progenitors in the developing mouse, we used in vitro derived pancreatic progenitors to determine direct targets of Sox9. We performed ChIP-seq analysis for Sox9 and determined its direct targets in the human genome. Using pancreatic progenitors that were derived from human embryonic stem cells, we were able to successfully find targets that were pancreas specific as well as those targets that are important in other endodermal lineages.

2015-08-07 | GSE61947 | GEO

Distinct regulatory programs for Sox9 in transcriptional regulation of the developing mammalian chondrocyte [RNA-seq]

Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly through a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with micorarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system. Overexpression of Sox9 with a control of EGFP in human fibroblasts to identify the direct targets of Sox9 regulatory system

2015-07-01 | E-GEOD-69110 | biostudies-arrayexpress

Distinct regulatory programs for Sox9 in transcriptional regulation of the developing mammalian chondrocyte [ChIP-seq]

Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly though a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with micorarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system. Overexpression of Sox9 with a control of EGFP in human fibroblasts to identify the direct targets of Sox9 regulatory system

2015-07-01 | E-GEOD-69109 | biostudies-arrayexpress

Distinct regulatory programs for Sox9 in transcriptional regulation of the developing mammalian chondrocyte [expression array]

Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly though a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with microrarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system

2015-07-01 | E-GEOD-69108 | biostudies-arrayexpress

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