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Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency

ABSTRACT: Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency

PROVIDER: PRJNA753865 | ENA |

REPOSITORIES: ENA

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Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency

Project description:Background & aims: Loss-of-function variants in the PTPN2 gene are associated with increased risk of inflammatory bowel disease. We recently showed that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice, restricting expansion of a small intestinal pathobiont associated with inflammatory bowel disease. Here, we aimed to identify how Ptpn2 loss affects ileal IEC subtypes and their function in vivo. Methods: Constitutive Ptpn2 wild-type, heterozygous, and knockout (KO) mice, as well as mice with inducible deletion of Ptpn2 in IECs, were used in the study. Investigation was performed using imaging techniques, flow cytometry, enteroid culture, and analysis of gene and protein levels of IEC markers. Results: Partial transcriptome analysis showed that expression of Paneth cell-associated antimicrobial peptides Lyz1, Pla2g2a, and Defa6 was down-regulated markedly in Ptpn2-KO mice compared with wild-type and heterozygous. In parallel, Paneth cell numbers were reduced, their endoplasmic reticulum architecture was disrupted, and the endoplasmic reticulum stress protein, C/EBP-homologous protein (CHOP), was increased in Ptpn2-KO mice. Despite reduced Paneth cell number, flow cytometry showed increased expression of the Paneth cell-stimulatory cytokines interleukin 22 and interferon γ+ in CD4+ T cells isolated from Ptpn2-KO ileum. Key findings in constitutive Ptpn2-KO mice were confirmed in epithelium-specific Ptpn2ΔIEC mice, which also showed impaired lysozyme protein levels in Paneth cells compared with Ptpn2fl/fl control mice. Conclusions: Constitutive Ptpn2 deficiency affects Paneth cell viability and compromises Paneth cell-specific antimicrobial peptide production. The observed effects may contribute to the increased susceptibility to intestinal infection and dysbiosis in these mice.

2023-04-10 | GSE181923 | GEO

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Cecum]

Project description:Loss-of-function variants in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene are associated with increased risk of inflammatory bowel disease (IBD). PTPN2 encodes T cell protein tyrosine phosphatase (TCPTP), a negative regulator of several intracellular signaling pathways including JAK-STAT. It has been shown that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice. However, the mechanisms by which Ptpn2 influences the intestinal flora are unknown. In this study, we aimed to identify how Ptpn2-loss affects the expression of genes associated with function/differentiation of IECs in the small and large intestines that could contribute to higher susceptibility to infection.

2023-08-02 | GSE181531 | GEO

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [ILEUM]

2023-04-06 | GSE181914 | GEO

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Proximal colon]

2023-08-02 | GSE181920 | GEO

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Distal Colon]

2023-08-02 | GSE181916 | GEO

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [ILEUM]

Project description:Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [ILEUM]

| PRJNA753852 | ENA

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Cecum]

Project description:Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Cecum]

| PRJNA753845 | ENA

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Proximal colon]

Project description:Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Proximal colon]

| PRJNA753863 | ENA

Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Distal Colon]

Project description:Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency [Distal Colon]

| PRJNA753858 | ENA

Differential gene expression in WT mice and mice lacking PTPN2 in T cells

Project description:WT mice and mice lacking PTPN2 in T cells (PTPN2-CD4Cre mice) were treated with AOM/DSS to induce colorectal tumours. RNA was isolated from tumour and non-tumour tissues in the colon. Colon samples from water-treated WT and PTPN2-CD4Cre mice served as additional control. Total RNA was isolated and the samples sequenced for polyA enriched RNA.

2020-10-03 | E-MTAB-9629 | biostudies-arrayexpress

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