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ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study

ABSTRACT: ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study

PROVIDER: PRJNA799370 | ENA |

REPOSITORIES: ENA

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ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine; a multi-omics study [ATAC-seq]

Project description:Microfold (M) cells reside in the intestinal epithelium of Peyer’s patches. Their unique ability to take up and transport antigens from the intestinal lumen to the underlying lymphoid tissue is key in the regulation of the gut-associated immune response. Here, we applied a multi-omics approach to investigate the molecular mechanisms that drive M cell differentiation in mouse small intestinal organoids. We generated a comprehensive profile of chromatin accessibility changes and transcription factor dynamics during in vitro M cell differentiation, allowing us to uncover numerous cell type-specific regulatory elements and associated transcription factors. By using single-cell RNA sequencing, we identified an M cell precursor population. We linked precursor-specific gene expression to transcription factor motif content in cis-regulatory elements with our newly developed computational tool SCEPIA, uncovering a high expression of and motif activity for the transcription factor ONECUT2. Subsequent in vitro and in vivo perturbation experiments revealed that ONECUT2 acts downstream of the RANK/RANKL signalling to support Enterocyte differentiation, thereby restricting M cell lineage specification. This study sheds new light on the mechanism regulating mucosal immunity and cell fate balance, and provides a powerful blueprint for investigation of cell fate switches in the intestinal epithelium.

2022-12-01 | GSE194183 | GEO

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine; a multi-omics study [ChIP-Seq]

2022-12-01 | GSE194182 | GEO

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine; a multi-omics study [scRNA-seq]

2022-12-01 | GSE194178 | GEO

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine; a multi-omics study [bulk RNA-seq]

2022-12-01 | GSE194177 | GEO

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [ATAC-seq]

Project description:ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [ATAC-seq]

| PRJNA799373 | ENA

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [ChIP-Seq]

Project description:ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [ChIP-Seq]

| PRJNA799374 | ENA

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [scRNA-seq]

Project description:ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [scRNA-seq]

| PRJNA799363 | ENA

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [bulk RNA-seq]

Project description:ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine a multi-omics study [bulk RNA-seq]

| PRJNA799357 | ENA

ONECUT2 regulates RANKL-dependent Enterocyte and Microfold cell differentiation in the small intestine; a multi-omics study

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

2022-12-01 | GSE194184 | GEO

ONECUT2 overexpression promotes RAS-driven lung adenocarcinoma progression

Project description:Aberrant differentiation, driven by activation of normally silent tissue-specific genes, results in a switch of cell identity and often leads to cancer progression. The underlying genetic and epigenetic events are largely unexplored. Here, we report ectopic activation of the hepatobiliary-, intestinal- and neural-specific gene one cut homeobox 2 (ONECUT2) in various subtypes of lung cancer. ONECUT2 expression was associated with poor prognosis of RAS-driven lung adenocarcinoma. ONECUT2 overexpression promoted the malignant growth and invasion of A549 lung cancer cells in vitro, as well as xenograft tumorigenesis and bone metastases of these cells in vivo. Integrative transcriptomics and epigenomics analyses suggested that ONECUT2 promoted the trans-differentiation of lung cancer cells by preferentially targeting and regulating the activity of bivalent chromatin domains through modulating Polycomb Repressive Complex 2 (PRC2) occupancy. Our findings demonstrate that ONECUT2 is a lineage-specific and context-dependent oncogene in lung adenocarcinoma and suggest that ONECUT2 is a potential therapeutic target for these tumors.

2019-12-27 | GSE102599 | GEO

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