Identifying interferon-stimulated genes enriched in multiple tissues of Irgm1-/- mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59603 | GEO | 2015/01/03
SECONDARY ACCESSION(S): PRJNA255751
REPOSITORIES: GEO
Similar Datasets
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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2023-10-01 | E-MTAB-13374 | biostudies-arrayexpress
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.
2011-10-02 | GSE27848 | GEO
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.
2011-10-02 | GSE27847 | GEO
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
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
Project description:Sjogren’s syndrome (SS) is a systemic autoimmune disease that targets the exocrine glands, resulting in impaired saliva and tear secretion. To date, type I interferons (I-IFNs) are increasingly recognized as pivotal mediators in SS, but their endogenous drivers have not been elucidated. Here, we investigate the role of mitochondrial double-stranded RNAs (mt-dsRNAs) in regulating I-IFNs and other glandular phenotypes of SS. We find that mt-dsRNAs are elevated in the saliva and tear of SS patients (n=73 for saliva and n=16 for tear) and in salivary glands of non-obese diabetic mice with salivary dysfunction. Using the in-house-developed 3D culture of immortalized human salivary gland cells, we show that stimulation by exogenous dsRNAs increase mt-dsRNAs, activate the innate immune system, trigger I-IFNs, and promote glandular phenotypes. These responses are mediated via the JAK1/STAT pathway. Indeed, a small chemical inhibitor of JAK1 attenuates mtRNA elevation and immune activation. We further show that muscarinic receptor ligand acetylcholine ameliorates autoimmune characteristics by preventing mt-dsRNA-mediated immune activation. Lastly, direct suppression of mt-dsRNAs reverses the glandular phenotypes of SS. Altogether, our study underscores the significance of mt-dsRNA upregulation in the pathogenesis of SS and suggests mt-dsRNAs as propagators of a pseudo-viral signal in the SS target tissue.
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Project description:The intestinal epithelium has a high turnover and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here we show that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, mTORC1 activation in macrophages protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism for optimizing proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as “commensals” that provide metabolic support to promote efficient self-renewal of the colon epithelium.
2023-08-08 | GSE175992 | GEO
Project description:We generated a novel Six2-Cre+/-PKAcaRfl/wt (CA-PKA) CA-PKA mouse in which expression of constitutive-active PKAcaR was induced in gastric mesenchyme progenitors. CA-PKA mice showed disruption of gastric homeostasis characterized by aberrant mucosal development and epithelial hyperproliferation; ultimately developing multiple features of gastric corpus preneoplasia including decreased parietal cells, mucous cell hyperplasia, spasmolytic peptide expressing metaplasia (SPEM) with intestinal characteristics and dysplastic and invasive cystic glands. Our results show that constitutively active PKAcaR in the stomach mesenchyme nonautonomously disrupts gastric homeostasis characterized by increased epithelial proliferation and aberrant epithelial maldevelopment, ultimately leading to gastric preneoplasia.
2022-09-20 | GSE196236 | GEO
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