Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA307544 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3081700.fastq.gz | Fastqsanger.gz | |||
| SRR3081710.fastq.gz | Fastqsanger.gz | |||
| SRR3081720.fastq.gz | Fastqsanger.gz | |||
| SRR3081701.fastq.gz | Fastqsanger.gz | |||
| SRR3081711.fastq.gz | Fastqsanger.gz |
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Project description:Pancreas lineage allocation and specifciation are regulated by sphingosine-1-phosphate signalling (13.5 and 15.5 dpc)
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Project description:Identifying the signals that regulate the survival, lineage allocation and specification of pancreas progenitors will help elucidate the embryonic origins of pancreas dysfunction and provide important cues for the efficient conversion of pluripotent stem cells into fully functional β cells. Several transcription factors regulating the conversion of the early pancreatic progenitors into terminally differentiated cells have been identified but extracellular signals regulating pancreas development are less well understood. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata and genomics we have found that sphingosine-1-phosphate signalling through plays a key role in this process. S1p signalling stabilizes the Hippo pathway effector YAP to promote progenitor survival, acinar and endocrine specification. Endocrine cell specification relies on Gai subunits revealing an unexpected dependence of lineage specification on selected intracellular signalling components. Independently of YAP stabilization, S1p signalling attenuates Notch levels, thus regulating lineage allocation. These findings identify S1p signalling as a key pathway coordinating cell survival, lineage allocation and specification during pancreas development.
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Project description:Identifying the signals that regulate the survival, lineage allocation and specification of pancreas progenitors will help elucidate the embryonic origins of pancreas dysfunction and provide important cues for the efficient conversion of pluripotent stem cells into fully functional β cells. Several transcription factors regulating the conversion of the early pancreatic progenitors into terminally differentiated cells have been identified but extracellular signals regulating pancreas development are less well understood. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata and genomics we have found that sphingosine-1-phosphate signalling through plays a key role in this process. S1p signalling stabilizes the Hippo pathway effector YAP to promote progenitor survival, acinar and endocrine specification. Endocrine cell specification relies on Gai subunits revealing an unexpected dependence of lineage specification on selected intracellular signalling components. Independently of YAP stabilization, S1p signalling attenuates Notch levels, thus regulating lineage allocation. These findings identify S1p signalling as a key pathway coordinating cell survival, lineage allocation and specification during pancreas development.
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Project description:We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies.
2020-04-14 | GSE121709 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
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Project description:Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis
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Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
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