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Identifying interferon-stimulated genes enriched in multiple tissues of Irgm1-/- mice

ABSTRACT: We observed enhanced epithelial proliferation secondary to elevated Type I IFNs in multiple tissues of Irgm1-/- mice. We discovered that Type I IFNs signaled through macrophages to promote this epithelial hyperproliferation. To determine candidate factors that could play a role in this process, we performed whole genome microarray analysis of salivary gland, small intestine, and isolated colonic macrophages of Irgm1-/- mice and C57BL/6 WT controls. Genes enriched in at least 2 of the 3 sample sources were then screened for the ability to augment epithelial proliferation in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE59603 | GEO | 2015/01/03

SECONDARY ACCESSION(S): PRJNA255751

REPOSITORIES: GEO

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Identifying interferon-stimulated genes enriched in multiple tissues of Irgm1-/- mice

Project description:We observed enhanced epithelial proliferation secondary to elevated Type I IFNs in multiple tissues of Irgm1-/- mice. We discovered that Type I IFNs signaled through macrophages to promote this epithelial hyperproliferation. To determine candidate factors that could play a role in this process, we performed whole genome microarray analysis of salivary gland, small intestine, and isolated colonic macrophages of Irgm1-/- mice and C57BL/6 WT controls. Genes enriched in at least 2 of the 3 sample sources were then screened for the ability to augment epithelial proliferation in vitro. RNA was extracted from three (small intestine and isolated colonic macrophage samples) or four (salivary gland samples) mice of each genotype (Irgm1-/- and WT). Both male and female six to nine week-old mice were used.

2015-01-03 | E-GEOD-59603 | biostudies-arrayexpress

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Project description:The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivalled capacity to drive tissue repair. Yet, the nature and role of macrophages in salivary gland homeostasis, and how they may contribute to tissue repair following injury is not well understood. Here, using scRNAseq we profile the transcriptomes of adult mouse salivary gland macrophages at steady state (D0) and at days 3 and 28 after targeted irradiation injury to define the transcriptional profiles of macrophages during homeostasis, acute injury and regeneration. We sorted epithelial cells (CD326+), endothelial cells (CD31+) and macrophages (CD45+CD11b+F4/80+) and sequenced their transcriptomes using 10x Genomics Single Cell 3' (v3.1). For each sample equal numbers of cells from 2 mice were pooled.

2023-10-01 | E-MTAB-13374 | biostudies-arrayexpress

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2)

Project description:The risk for colon cancer is associated with nutrition, especially high fat and low calcium diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation. C57BL/6 mice received a Westernized high fat and low calcium diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. RNA was isolated from colon scrapings and subjected to gene expression profiling (n=7 control mice and n=9 heme-fed mice).

2011-10-01 | E-GEOD-27848 | biostudies-arrayexpress

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2)

2011-10-02 | GSE27848 | GEO

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 1)

2011-10-02 | GSE27847 | GEO

Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 1)

Project description:The risk for colon cancer is associated with nutrition, especially with diets high in red meat. Red meat contains the iron porphyrin pigment heme, which induces cytotoxicity of the colon contents and epithelial hyperproliferation. Using a mouse model, we showed that heme caused damage to the colonic surface epithelium and induced compensatory hyperproliferation. Expression levels of heme- and stress-related genes show that heme affects surface cells and not directly crypt cells. Therefore, injured surface cells should signal to crypt TA cells to induce compensatory hyperproliferation. Surface-specific downregulated inhibitors of proliferation were Wnt inhibitory factor 1, Indian Hedgehog, Bone morphogenic protein 2 and possibly Interleukin-15. Heme also upregulated Amphiregulin, Epiregulin and Cyclooxygenase-2 mRNA in the surface cells, however, their protein/metabolite levels were not increased as heme induced surface-specific translation repression by increasing 4E-BP1. Therefore, we conclude that heme induced colonic hyperproliferation and hyperplasia by repressing feedback inhibition of proliferation. C57BL/6 mice received a Westernized diet with or without heme (the polyporphyrin pigment of red meat). Mice received control or heme diet for 14 days. After 14 days, mice were sacrificed and colons were taken out. Swiss rolls were made from the middle 2 cm of the colon. These rolls were used for LCM, and surface cells and crypts cells were separately isolated. RNA was isolated from surface and crypt cells and subjected to gene expression profiling (n=4 control mice and n=3 heme-fed mice).

2011-10-01 | E-GEOD-27847 | biostudies-arrayexpress

Mitochondrial double-stranded RNAs as a pivotal mediator in the pathogenesis of Sjogren’s syndrome

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2022-10-05 | GSE168148 | GEO

Protein Kinase A (PKAc alpha ) regulates gastric homeostasis and preneoplastic lesions

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2022-09-20 | GSE196236 | GEO

RNA-seq analysis of sorted colon epithelial cells and colon lamia propria macrophages from mice where Tsc2 is deleted in Lyz2-expressing cells

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2023-08-08 | GSE175992 | GEO

Interferons disrupt lung epithelial repair during recovery from respiratory infection [RN200717]

Project description:Respiratory viral infections cause lung epithelial damage, barrier dysfunction and severe disease. Type I interferons (IFN-a/b) are antiviral cytokines whose therapeutic use is limited by well-characterized pleiotropic effects. Type III IFNs (IFN-λ) are less pro-inflammatory and regarded a superior treatment option. Here, we show that IFN signalling reduces lung epithelial proliferation and differentiation and increases epithelial apoptosis during recovery from viral infection. This delays epithelial repair, increasing disease severity and the risk of bacterial superinfection. IFN-a has least effects, with IFN-b intermediate and IFN-λ strongest action.

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