Single-cell RNA-Seq analysis of colonic mesenchyme lacking tumor necrosis factor receptor 1
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PROVIDER: PRJNA747926 | ENA |
REPOSITORIES: ENA
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Project description:RNA-Seq analysis of colonic mesenchyme lacking tumor necrosis factor receptor 1
| PRJNA748108 | ENA
Project description:Our study reports a role for tumor necrosis factor receptor 1 (TNFR1) in maintaining colonic mesenchymal cell diversity. Through scRNA-seq profiling, we show that a TNFR1-deficient mesenchyme has a reduced transcriptional diversity of mesenchymal cell populations, with a near complete loss of a cluster enriched in TNF, IFN, and cytokine signaling genes, which include MMP9, CD200, TNFRSF9, and TRAF1. We show that the transcriptional clustering of mesenchymal cells is consistently distinct and unique to the TNFR1-/- genotype. TNFR1-/- mesenchymal cells cluster as a single population, compared to control mesenchymal cells that cluster into 3 sub-populations. Through in vivo immunostaining in control and TNFR1-/- mice we show that the TNF signaling cluster localizes to the sub-epithelial niche and therefore may play an important role in the crosstalk between epithelial stem cells and mesenchyme-driven immune signaling in health and disease.
2025-07-01 | GSE180346 | GEO
Project description:Our study reports a role for mesenchymal TNFR1 in maintaining colonic mesenchymal cell diversity and facilitation of a function epithelial stem cell niche. Through RNA-seq profiling, we show that a TNFR1-deficient mesenchyme has altered anchoring and cell substrate junctions, focal adhesions, extracellular matrix, and actin binding processes. We find specific reduction in the key stem cell niche factor, RSPO3, crucial for Lgr5+ stem cell maintenance, downregulated 5.1-fold in the TNFR1 deficient mesenchyme. Pathways classically associated with proliferation and differentiation, including Phosphoinositide 3-kinase (P13k) and Mitogen-activated protein kinase (MAPK), and those involved in migration, namely Ras-proximate-1 or Ras-related protein 1 (RAP1), TGF-β and RAS, were significantly enriched in TNFR1-/- mesenchyme compared to controls. In particular, Itga6, representing the integrin alpha 6 subunit, was one of the most highly upregulated transcripts. Therefore, the transcriptome profiling of the TNFR1 deficient mesenchyme deletion suggests an important role for TNFR1 in the regulation of mesenchymal cell-matrix interactions and niche transcript expression.
2023-11-01 | GSE180421 | GEO
Project description:Colonic epithelial repair is a key determinant of health. After injury, repair initiates through phenotypic reprogramming of wounded epithelium to a regenerative state permissive for the activation of alternative stem cell populations and healing. Although cytokine signals such as interferon help induce regenerative reprogramming, the signals that modify this state as the wound resolves remain largely unknown. Here we show that, during healing, the late upregulation of a cytokine receptor, tumor necrosis factor (TNF) receptor 2 (R2, TNFR2, Tnfrsf1b), clears the phenotype of regenerative signaling and restores homeostatic patterns of epithelial differentiation. Mice lacking epithelial-specific expression of TNFR2 also failed to complete colon ulcer healing, suggesting that full repair requires coordination of both regenerative and homeostatic epithelial phenotypes. In single-cell RNA-seq experiments, we find that colonic epithelial organoids grown from Tnfr2-/- mice retain a highly enriched census of progenitor cells and reduced representation of differentiated cells, consistent with TNFR2's role in promoting differentiation. These results demonstrate how epithelial cells adapt to inflammatory cues to choreograph repair.
2023-08-22 | GSE230816 | GEO
Project description:Single-cell analysis of colonic organoids deficient for tumor necrosis factor receptor 2
| PRJNA962604 | ENA
Project description:Colonic epithelial repair is a key determinant of health. After injury, repair initiates through phenotypic reprogramming of wounded epithelium to a regenerative state permissive for the activation of alternative stem cell populations and healing. Although cytokine signals such as interferons may help induce regenerative reprogramming, the signals that modify this state as the wound resolves remain largely unknown. Here we examined whether cytokine signaling mediated by tumor necrosis factor receptor 2 (TNFR2) influenced the wound repair process. We examined mice with targeted deletion of the Tnfrsf1b (TNFR2) gene in intestinal/colonic epithelium (Vil1::Cre;Tnfr2-f/f) and compared their transcriptional profiles to control (Tnfr2-f/f) mice. We sorted EpCAM+ (epithelial) cells from Vil1::Cre;Tnfr2-f/f and control DSS-treated mice and performed bulk RNA-Seq. Comparison of transcript expression profile before and after DSS-induced colitis in control (Tnfr2-f/f) mice revealed upregulation of pathways associated with metabolic regulation, ribosomal function, oxidative stress, TNF signaling, and focal adhesions after DSS treatment. Pathway enrichment analysis demonstrated elevated regenerative (“fetal”) intestinal signaling, reduced inflammation, and increased proliferative signaling in Vil1::Cre;Tnfr2-f/f colonic epithelium after DSS treatment. The knockout epithelium also showed reduced expression of markers of differentiated colonic epithelium and elevated expression of progenitor cell signaling. Thus, the transcriptional data were consistent with increased regenerative signaling in TNFR2-knockout epithelium, suggesting that TNFR2 has a role in restraining the relatively undifferentiated regenerative state.
2023-08-22 | GSE230329 | GEO
Project description:10x Chromium single cell RNA-Seq of colonic mesenchyme cell populations in health and Ulcerative Colitis in human patients and health in DSS-induced colitis in murine colon
2018-09-27 | GSE114374 | GEO
Project description:Single cell RNA sequencing of the mouse colonic mesenchyme. Mesenchymal/lamina propria cells were isolated from the middle and distal colon of wild type mice and were pooled. The vast majority of intestinal epithelial cells were depleted by Ethylenediaminetetraacetic acid (EDTA) treatment of the tissue samples and mesenchymal/lamina propria cells were isolated after enzymatic treatment with collagenase XI and dispase. Single cell RNA sequencing was performed with the Drop-seq protocol.
2021-10-14 | GSE185638 | GEO
Project description:Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease
| PRJNA377154 | ENA
Project description:Single cell RNA sequencing of the mouse colonic mesenchyme. Mesenchymal/lamina propria cells were isolated from the middle and distal colon of wild type mice in two biological replicates. For each biological replicate the colons of n = 2 mice were pooled. The vast majority of intestinal epithelial cells were depleted by Ethylenediaminetetraacetic acid (EDTA) treatment of the tissue samples and mesenchymal/lamina propria cells were isolated after enzymatic treatment with collagenase XI and dispase. Single cell RNA sequencing was performed with the Drop-seq protocol. N =5 Drop-seq collections (samples) were processed in total, two from the first biological replicate and three from the second.
2019-12-21 | GSE142423 | GEO