Expression profiling of Irgm1-/- (Lrg-47) HSCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11591 | GEO | 2011/06/23
SECONDARY ACCESSION(S): PRJNA106227
REPOSITORIES: GEO
Similar Datasets
Project description:To assess gene expression changes in Irgm1 (Lrg-47) deficient HSCs Keywords: genetic modification, knockout A total of 6 samples were analyzed: 3 experimental replicates of Irgm1 HSCs were compared with 3 control replicates of WT HSCs
2011-06-22 | E-GEOD-11591 | biostudies-arrayexpress
Project description:Polymorphisms in the IRGM gene are associated with susceptibility to tuberculosis in humans. A murine ortholog of Irgm, Irgm1, is also essential for controlling Mycobacterium tuberculosis (Mtb) infection in mice. Multiple processes have been associated with IRGM1 activity that could impact the host response to Mtb infection, including roles in autophagy-mediated pathogen clearance and expansion of activated T cells. However, what IRGM1-mediated pathway is necessary to control Mtb infecion in vivo and the mechanistic basis for this control remains unknown. We dissected the contribution of IRGM1 to immune control of Mtb pathogenesis in vivo and found that Irgm1 deletion leads to higher levels of IRGM3-dependent type I interferon signaling. The increased type I interferon signaling precludes T cell expansion during Mtb infection. The absence of Mtb-specific T cell expansion in Irgm1 -/- mice results in uncontrolled Mtb infection in neutrophils and alveolar macrophages, which directly contributes to susceptibility to infection. Together, our studies reveal that IRGM1 is required to promote T cell-mediated control of Mtb infection in neutrophils, which is essential for the survival of Mtb-infected mice. These studies also uncover new ways type I interferon signaling can impact TH1 immune responses.
2024-07-31 | GSE271425 | GEO
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.
2015-01-03 | GSE59603 | GEO
Project description:The human IRGM gene has been linked to inflammatory diseases including sepsis and Crohn’s disease. Decreased expression of human IRGM, or of the mouse orthologues Irgm1 and Irgm2, leads to increased production of a number of inflammatory chemokines and cytokines in vivo and/or in cultured macrophages. Prior work has indicated that increased cytokine production is instigated by metabolic alterations and by changes in mitochondrial homeostasis; however, a comprehensive mechanism has not been elucidated. In the studies presented here, RNA deep sequencing and quantitative PCR were used to show that increases in cytokine production, as well as most changes in the transcriptional profile of Irgm1-/- bone marrow-derived macrophages (BMM), are dependent on increased type I IFN production seen in those cells. Metabolic alterations that drive increased cytokines in Irgm1-/- BMM - specifically increases in glycolysis and increased accumulation of acyl-carnitines - were unaffected by quenching type I IFN signaling. Dysregulation of peroxisomal homeostasis was identified as a novel upstream pathway that governs type I IFN production and inflammatory cytokine production. Collectively, these results enhance our understanding of the complex biochemical changes that are triggered by lack of Irgm1 and contribute to inflammatory disease seen with Irgm1-deficiency.
2024-12-26 | GSE276820 | GEO
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
Project description:Background & Aims: Hierarchical organization of intestine relies on their stem cells by self-renew and producing committed progenitors. Although signals like Wnt are known to animate the continued renewal by maintaining intestinal stem cells (ISCs) activity, molecular mechanisms especially E3 ubiquitin ligases that modulate ISCs ‘stemness’ and supportive niche have not been well understood. Here, we investigated the role of Cullin 4B (Cul4b) in regulating ISC functions. Methods: We generated mice with intestinal epithelial-specific disruption of Cul4b (pVillin-cre; Cul4bfn/Y), inducible disruption of Cul4b (Lgr5-creERT2; Cul4bfn/Y, CAG-creERT2; Cul4bfn/Y) and their control (Cul4bfn/Y). Intestinal tissues were analyzed by histology, immunofluorescence, RNA sequencing and mass spectrum. Intestinal organoids deprived from mice with pVillin-Cre; Cul4bfn/Y, Lgr5-Cre; Cul4bfn/Y, Tg-Cul4b and their controls were used in assays to measure intestinal self-renewal, proliferation and differentiation. Wnt signaling and intestinal markers were analyzed by immunofluorescence and immunoblot assays. Differential proteins upon Cul4b ablation or Cul4b-interacting proteins were identified by mass spectrometry. Results: Cul4b specifically located at ISCs zone. Block of Cul4b impaired intestinal homeostasis maintenance by reduced self-renewal and proliferation. Transcriptome analysis revealed that Cul4b-null intestine lose ISC characterization and showed disturbed ISC niche. Mechanistically, reactivated Wnt pathway could recover intestinal dysfunction of Cul4b knockout mice. Analysis of differential total and ubiquitylated proteins uncovered the novel targeting substrate of Cullin-Ring ubiquitin ligase 4b (CRL4b), immunity-related GTPase family M member 1 (Irgm1) in intestine. Decreased Irgm1 rescued abnormally interferon signaling, overemphasized autophagy and downstream phosphate proteins in Cul4b knockout mice. Conclusion: We conclude that Cul4b is essential for ISC self-renewal and Paneth cell function by targeting Irgm1 and modulating Wnt signaling. Our results demonstrate that Cul4b is a novel ISC stemness and niche regulator.
2022-08-11 | PXD021528 | Pride
Project description:Gene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs. Analysis of gene expression of bone marrow-derived CD45.2+ CD150+cKit+Sca-1+CD4-CD8a-CD19-B220-Gr-1- HSCs from congenic recipient animals transplanted >20 weeks with either wild-type or Satb1-deficient hematopoeitic cells.
2013-04-07 | E-GEOD-44107 | biostudies-arrayexpress
Project description:The balance of self-renewal and differentiation is crucial to ensure the homeostasis of the hematopoietic system, and is a key hallmark of hematopoietic stem cells (HSCs); however, the underlying molecular pathways are not completely understood, including the role of micro-RNAs. To assess micro-RNA contributions, we performed micro-RNA profiling of HSCs and their immediate downstream progeny multi-potent progenitors (MPPs) from wild type control and Pbx1-conditional knockout mice, whose HSCs display a profound self-renewal defect.
2019-04-01 | GSE113062 | GEO
Project description:To understand the molecular mechanism by which Irgm1 controls innate immune homoestasis
2020-09-01 | E-MTAB-9164 | biostudies-arrayexpress