Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA173774 | ENA |
REPOSITORIES: ENA
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Project description:Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis. Comparison of KO vs. WT with five replications per treatment sample
2013-08-09 | E-GEOD-40368 | biostudies-arrayexpress
Project description:Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.
2013-08-09 | GSE40368 | GEO
Project description:Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet β-cell Endoplasmic Reticulum Stress and Proliferation
| PRJNA296080 | ENA
Project description:Ablation of coactivator Med1 regulates bulge keratinocyte stem cells and accelerates epidermal regeneration after injury [10wk keratinocyte]
| PRJNA218223 | ENA
Project description:Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates basic cell functions through metabolic and signaling pathways. Intracellular metabolism of S1P is controlled, in part, by two homologous S1P phosphatases, 1 and 2, which are encoded by Sgpp1 and Sgpp2, respectively. S1P phosphatase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. S1P phosphatase 1 is important for skin homeostasis, but little is known about the functional role of S1P phosphatase 2. To identify the functions of S1P phosphatase 2 in vivo, we studied mice with the Sgpp2 gene deleted. In contrast to Sgpp1-/- mice, Sgpp2-/- mice had normal skin and were viable into adulthood. Unexpectedly, WT mice expressed Sgpp2 mRNA at high levels in pancreatic islets when compared with other tissues. Sgpp2-/- mice had normal blood insulin levels and pancreatic islet size; however, Sgpp2-/- mice treated with a high-fat diet (HFD) had significantly lower blood insulin levels and smaller pancreatic islets compared with WT mice. The smaller islets in the HFD-treated Sgpp2-/- mice had a significantly lower adaptive B-cell proliferation rate in response to the diet compared with HFD-treated WT mice. Importantly, B-cells from Sgpp2-/- mice fed a normal diet showed significantly increased expression of proteins characteristic of the endoplasmic reticulum (ER) stress response compared with B-cells from WT mice. Our results suggest that Sgpp2 deletion causes B-cell ER stress, which is a known cause of B-cell dysfunction, and reveal a novel juncture in the sphingolipid recycling pathway that could impact the development of diabetes. Three replications of Mouse (WT vs KO) that were treated with with Normal and HFD foods.
2016-07-25 | E-GEOD-73131 | biostudies-arrayexpress
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.
| S-EPMC8784167 | biostudies-literature
Project description:Progenitor cells at the basal layer of skin epidermis play an essential role in maintaining tissue homeostasis and enhancing wound repair in skin. The proliferation, differentiation, and cell death of epidermal progenitor cells have to be delicately regulated, as deregulation of this process can lead to many skin diseases, including skin cancers. However, the underlying molecular mechanisms involved in skin homeostasis remain poorly defined. In this study, with quantitative proteomics approach, we identified an important interaction between KDF1 (Keratinocyte Differentiation Factor 1) and IKKα (IκB kinase α) in differentiating skin keratinocytes. Ablation of either KDF1 or IKKα in mice leads to similar but striking abnormalities in skin development, particularly in skin epidermal differentiation. With biochemical and mouse genetics approach, we further demonstrate that the interaction of IKKα and KDF1 is essential for epidermal differentiation. To probe deeper into the mechanisms, we find that KDF1 associates with a deubiquitinating protease, USP7 (Ubiquitin Specific Peptidase 7), and KDF1 can regulate skin differentiation through deubiquitination and stabilization of IKKα. Taken together, our study unravels an important molecular mechanism underlying skin tissue homeostasis and epidermal differentiation.
2020-05-13 | PXD015673 | Pride
Project description:Several long non-coding RNAs (lncRNAs) act as regulators of cellular homeostasis; however, few of these molecules were functionally characterized in a mature human tissue environment. Here, we report that the lncRNA LINC00941 is a crucial regulator of human epidermal homeostasis. LINC00941 is enriched in progenitor keratinocytes and acts as a repressor of keratinocyte differentiation. Furthermore, LINC00941 represses SPRR5, a previously uncharacterized molecule, which functions as an essential positive regulator of keratinocyte differentiation. Interestingly, 54.8% of genes repressed in SPRR5 deficient epidermal tissue are induced in LINC00941 depleted organotypic epidermis, suggesting a common mode of action for both molecules.
2019-01-28 | GSE118077 | GEO