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SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE148695 | GEO | 2021/10/05

REPOSITORIES: GEO

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SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling.

Project description:Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5+ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.

| S-EPMC8741647 | biostudies-literature

SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

Project description:SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

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scRNA-Seq of Intestine Epithelia (Ileum and Colon) from Satb2-deficient and WT mice

Project description:The goal of this study is to study signal cell transcripton level changes after Satb2 gene loss in the colonic epithelium.

2021-10-05 | GSE148693 | GEO

ATAC-seq of Intestine Epithelia (Ileum and Colon) from Satb2-deficient and WT mice

Project description:The goal of this study is to study the chromatin accessibility signature after Satb2 gene loss in the colonic epithelium.

2021-10-05 | GSE148690 | GEO

The lipid kinase PI4KIII? preserves lysosomal identity.

Project description:Lipid modifications are essential in cellular sorting and trafficking inside cells. The role of phosphoinositides in trafficking between Golgi and endocytic/lysosomal compartments has been extensively explored and the kinases responsible for these lipid changes have been identified. In contrast, the mechanisms that mediate exit and recycling from lysosomes (Lys), considered for a long time as terminal compartments, are less understood. In this work, we identify a dynamic association of the lipid kinase PI4KIII? with Lys and unveil its regulatory function in lysosomal export and retrieval. We have found that absence of PI4KIII? leads to abnormal formation of tubular structures from the lysosomal surface and loss of lysosomal constituents through these tubules. We demonstrate that the kinase activity of PI4KIII? is necessary to prevent this unwanted lysosomal efflux under normal conditions, and to facilitate proper sorting when recycling of lysosomal material is needed, such as in the physiological context of lysosomal reformation after prolonged starvation.

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Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing.

Project description:Chronic inflammation is often associated with the development of tissue fibrosis, but how mesenchymal cell responses dictate pathological fibrosis versus resolution and healing remains unclear. Defining stromal heterogeneity and identifying molecular circuits driving extracellular matrix deposition and remodeling stands to illuminate the relationship between inflammation, fibrosis, and healing. We performed single-cell RNA-sequencing of colon-derived stromal cells and identified distinct classes of fibroblasts with gene signatures that are differentially regulated by chronic inflammation, including IL-11-producing inflammatory fibroblasts. We further identify a transcriptional program associated with trans-differentiation of mucosa-associated fibroblasts and define a functional gene signature associated with matrix deposition and remodeling in the inflamed colon. Our analysis supports a critical role for the metalloprotease Adamdec1 at the interface between tissue remodeling and healing during colitis, demonstrating its requirement for colon epithelial integrity. These findings provide mechanistic insight into how inflammation perturbs stromal cell behaviors to drive fibroblastic responses controlling mucosal matrix remodeling and healing.

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Ileum and colon goblet cell proteome

Project description:This study is a comparative proteomics study of FACS sorted Muc2 expressing and non expressing cells in mouse ileum and colon.

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Bulk RNA-seq (>20M reads) of Intestine Epithelium (Ileum and Colon) from Satb2-deficient and WT mice

Project description:Resequening ileum and colon epithelium with deeper reads to evaluate consequence of Satb2 gene loss in the colonic epithelium. The same library construction method was used to compare with Bulk RNA-seq data from In Vitro cultured mouse organoids.

2021-10-05 | GSE167284 | GEO

Bulk RNA-seq of 3D Cultured Intestinal Organoids (Ileum and Colon) from Satb2-deficient and WT mice

Project description:The colonic microenvironment may have influenced gene expression of the ileal-like mucosa in Satb2KO colon In Vivo. We use 3D culture organoid system In Vitro to mitigate the environmental influence.

2021-10-05 | GSE167281 | GEO

Bulk RNA-seq of Intestine Epithelia (Jejunum, Ileum, Cecum and Colon) from Satb2-deficient and WT mice

Project description:The goal of this study is to study the consequence of Satb2 gene loss in the colonic epithelium.

2021-10-05 | GSE148692 | GEO