Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Essential role of Arid1a in intestinal stem cell maintenance and homeostasis through Sox9 regulation

ABSTRACT: Essential role of Arid1a in intestinal stem cell maintenance and homeostasis through Sox9 regulation

PROVIDER: PRJNA433040 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Essential role of Arid1a in intestinal stem cell maintenance and homeostasis through Sox9 regulation (ChIP-Seq)

Project description:Arid1a, a subunit of the SWI/SNF chromatin remodeling complex, have been reported in multiple human cancers, however, its functional role in intestinal homeostasis remains unclear. To investigate the role of Arid1a in murine intestine, we have employed ChIP experiments in intestinal spheroid cells generated from crypt cells of wild type mice. ChIP assay revealed that Arid1a binds directly to the Sox9 promoter to support its expression.

2018-10-24 | GSE121658 | GEO

Essential role of Arid1a in intestinal stem cell maintenance and homeostasis through Sox9 regulation (ChIP-Seq)

Project description:Essential role of Arid1a in intestinal stem cell maintenance and homeostasis through Sox9 regulation (ChIP-Seq)

| PRJNA498053 | ENA

Essential role of Arid1a in intestinal stem cell maintenance and homeostasis through Sox9 regulation

Project description:Arid1a, a subunit of the SWI/SNF chromatin remodeling complex, have been reported in multiple human cancers, however, its functional role in intestinal homeostasis remains unclear. To investigate the role of Arid1a in murine intestine, we have employed whole genome microarray expression profiling of Arid1a conditional knock out mouse intestines. We found that Wnt signaling is downregulated in Arid1a conditional knock out mouse intestines compared to that of wild type mouse intestines.

2018-02-06 | GSE110181 | GEO

Endometrial epithelial Arid1a is essential in early pregnancy

Project description:Endometrial epithelial Arid1a is necessary for normal gene expression and maintenance of a receptive endometrium at pre-implantation stage in mice. We used RNA-sequencing to determine the differences in uterine gene expression resulting from deletion of endometrial epithelial Arid1a.

2022-03-01 | GSE196489 | GEO

Arid1a is essential for endometrial gland development

Project description:Arid1a is essential for endometrial gland development

| PRJNA564689 | ENA

A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and non-essential modes of oncogenic transformation

Project description:Mutations in ARID1A, encoding a subunit of the BAF chromatin remodeling complex, rank amongst the most common molecular aberrations in human cancer. However, oncogenic consequences of ARID1A mutation in human cells remain poorly defined due to lack of forward human genetic model systems. Here, CRISPR/Cas9 knockout of ARID1A in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity and mucinous differentiation but impaired Wnt/b-catenin signaling. Genetic Wnt pathway activation rescued mucinous differentiation, but not hyperproliferation, suggesting alternative essential pathways of ARID1A-mediated transformation. ARID1A loss induced transcriptional regulatory modules characteristic of MSI and EBV subtype human gastric cancer, including FOXM1 regulation of multiple mitotic regulatory genes and BIRC5/survivin. Convergently, high-throughput compound screening indicated selective vulnerability of ARID1A-deficient organoids to BIRC5/survivin inhibition, functionally implicating BIRC5/survivin as an essential mediator of proliferation following initial ARID1A loss. However, CRISPR inactivation of ARID1A in established gastric cancer cell lines did not elicit sensitivity to BIRC5/survivin inhibitors, suggesting that this pathway may be selectively required during the early establishment of tumorigenesis. Overall, we define distinct pathways downstream of oncogenic ARID1A mutation, with non-essential Wnt-inhibited mucinous differentiation in parallel with essential transcriptional FOXM1/BIRC5-stimulated proliferation, indicating the general utility of organoid-based forward genetic cancer analysis in human cells.

2021-01-05 | GSE164179 | GEO

Endometrial epithelial Arid1a is essential in early pregnancy

Project description:Endometrial epithelial Arid1a is essential in early pregnancy

| PRJNA805186 | ENA

Arid1a is essential for intestinal stem cells through Sox9 regulation.

Project description:Inactivating mutations of Arid1a, a subunit of the Switch/sucrose nonfermentable chromatin remodeling complex, have been reported in multiple human cancers. Intestinal deletion of Arid1a has been reported to induce colorectal cancer in mice; however, its functional role in intestinal homeostasis remains unclear. We investigated the functional role of Arid1a in intestinal homeostasis in mice. We found that intestinal deletion of Arid1a results in loss of intestinal stem cells (ISCs), decreased Paneth and goblet cells, disorganized crypt-villous structures, and increased apoptosis in adult mice. Spheroids did not develop from intestinal epithelial cells deficient for Arid1a Lineage-tracing experiments revealed that Arid1a deletion in Lgr5+ ISCs leads to impaired self-renewal of Lgr5+ ISCs but does not perturb intestinal homeostasis. The Wnt signaling pathway, including Wnt agonists, receptors, and target genes, was strikingly down-regulated in Arid1a-deficient intestines. We found that Arid1a directly binds to the Sox9 promoter to support its expression. Remarkably, overexpression of Sox9 in intestinal epithelial cells abrogated the above phenotypes, although Sox9 overexpression in intestinal epithelial cells did not restore the expression levels of Wnt agonist and receptor genes. Furthermore, Sox9 overexpression permitted development of spheroids from Arid1a-deficient intestinal epithelial cells. In addition, deletion of Arid1a concomitant with Sox9 overexpression in Lgr5+ ISCs restores self-renewal in Arid1a-deleted Lgr5+ ISCs. These results indicate that Arid1a is indispensable for the maintenance of ISCs and intestinal homeostasis in mice. Mechanistically, this is mainly mediated by Sox9. Our data provide insights into the molecular mechanisms underlying maintenance of ISCs and intestinal homeostasis.

| S-EPMC6358682 | biostudies-literature

Arid1a is essential in cardiomyocytes for neonatal heart maturation

Project description:Arid1a is essential in cardiomyocytes for neonatal heart maturation

| PRJNA648412 | ENA

Klf9 is essential for cardiac mitochondrial homeostasis

Project description:Klf9 is essential for cardiac mitochondrial homeostasis

| PRJNA1166649 | ENA