A profile of murine thymocytes from mice hypomorphic for Atg16l1
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12707 | GEO | 2008/09/10
SECONDARY ACCESSION(S): PRJNA112727
REPOSITORIES: GEO
Similar Datasets
Project description:The aim of this study is to survey global gene expression of total thymocytes from wild-type mice and Atg16l1 mutant (hypomorph) mice. Experiment Overall Design: Total RNA was extracted from total thymocytes from the following samples and analyzed: Experiment Overall Design: Atg16l1 hypomorph: 2 mice (7 weeks), 1 male and 1 female Experiment Overall Design: Control: 2 mice (7 weeks), 1 male and 1 female Experiment Overall Design: Global gene expression profiling was performed using Affymetrix technology. The animals used were independent of each other.
2008-10-25 | E-GEOD-12707 | biostudies-arrayexpress
Project description:Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells. Experiment Overall Design: 4 Samples: 2 replicates of Atg16-hypomorph Paneth cells and 2 replicates of Wildtype Paneth cells.
2008-11-15 | E-GEOD-13512 | biostudies-arrayexpress
Project description:Themis1, a recently described T-lineage specific protein, is essential for thymic positive and negative selection. Although Themis1 has been clearly identified as a component of the T cell antigen receptor (TCR) signalosome, its precise role in TCR signaling remains unclear. Here, we used quantitative proteomic and TCR signaling reporter mice to gain insight into Themis1 signaling function. Mass spectrometry analysis of the Themis1 interactome identified Grb2, SHP1 and Vav1 as the principal interacting partners of Themis1 in thymocytes. The dataset contains mass spectrometry results from the analysis of 6 different kind of AP-MS purifications (based on immunoprecipitation using a Themis1 antibody) starting from the following samples: - thymocytes from WT mice, non stimulated (noted WT NS) - thymocytes from WT mice, stimulated with pervanadate (noted WT P) - thymocytes from GRB2 +/- mice (with decreased expression of GRB2), non stimulated (noted GRB2 NS) - thymocytes from GRB2 +/- mice (with decreased expression of GRB2), stimulated with pervanadate (noted GRB2 P) - thymocytes from Themis1 -/- mice (knock-out for Themis1), non stimulated (noted KO NS) - thymocytes from Themis1 -/- mice (knock-out for Themis1), stimulated with pervanadate (noted KO P) Three biological replicates were prepared for these 6 different conditions (noted, 1,2,3), yielding 18 analyzed samples. Three technical nanoLC-MS runs were acquired for each sample (noted R1, R2, R3), leading to the 54 nanoLC-MS raw files contained in the dataset.
2017-02-06 | PXD004072 | Pride
Project description:Bcl11b hypomorphic mutant thymocytes
| PRJNA356604 | ENA
Project description:The clear role of autophagy in human inflammatory diseases such as Crohn’s disease was first identified by genome-wide association studies and subsequently dissected in multiple mechanistic studies. ATG16L1 has been particularly well studied in knockout and hypomorph settings as well as models recapitulating the Crohn’s disease-associated T300A polymorphism. Interestingly, ATG16L1 has a single homolog, ATG16L2, which is independently implicated in diseases including Crohn’s disease and systemic lupus erythematosus. However, the contribution of ATG16L2 to canonical autophagy pathways and other cellular functions is poorly understood.To better understand its role, we generate and analyze the first, to our knowledge, ATG16L2 knockout mouse. Our results show that ATG16L1 and ATG16L2 contribute very distinctly to autophagy and cellular ontogeny in myeloid, lymphoid and epithelial lineages. Dysregulation of any of these lineages could contribute to complex diseases like Crohn’s disease and systemic lupus erythematosus, highlighting the value of examining cell-specific effects. We also identify a novel genetic interaction between ATG16L2 and epithelial ATG16L1. These findings are discussed in the context of how these genes may contribute distinctly to human disease.
2019-07-13 | GSE134226 | GEO
Project description:In order to unravel the functional role of autophagy in skin homeostasis, we performed single-cell RNA-sequencing on total skin of 10-weeks-old male mice lacking ATG16L1 selectively in keratinocytes. Keratinocyte-specific ATG16L1 knock-out (KO) mice do not show an overt skin phenotype. By performing single-cell analysis on total skin of control mice and mice lacking ATG16L1 in keratinocytes, we could identify a crucial role for keratinocyte autophagyin mediating the timing of hair follicle stem cell activation in hair growth.
2023-07-13 | GSE218854 | GEO
Project description:genomic profiling of murine thymocytes of Atm deficient mice with and without T-cell lymphoma Keywords: genetic modification
2008-07-15 | GSE10844 | GEO
Project description:murine DP thymocytes transcriptome
| PRJNA804863 | ENA
Project description:Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.
2008-11-08 | GSE13512 | GEO
Project description:Review on the role of Bcl11b in thymus and periphery and impact on diseases RNA was extracted from DP thymocytes of bcl11bf/fCd4cre/tcra-/- and tcra-/- mice. Tcra-/- mice only have preselected DP thymocytes. Such mice were used to determine the role of Bcl11b before selection, considering the defective positive selection in bcl11bf/fcd4cre mice. RNA was isolated and submitted for library generation and microarray analysis to determine expression profile of bcl11b-/- preselected DP thymocytes.
2014-04-12 | E-GEOD-56714 | biostudies-arrayexpress