Mus musculus
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ABSTRACT:
PROVIDER: PRJNA137541 | ENA |
REPOSITORIES: ENA
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Project description:Epidermal stem cells ensure that skin homeostasis is maintained. In murine skin, epidermal stem cells cluster at specific niches where, under steady-state conditions, they undergo cycles of dormancy and activation1. When cellular replenishment is required, epidermal stem cells egress from the niche and proliferate for a limited number of times to subsequently feed into the differentiated compartment1-3. However, only a subset of stem cells becomes active during each round of morphogenesis, suggesting that stem cells coexist in heterogeneous responsive states within the same niche. Using a circadian clock fluorescent reporter mouse model, we show that the dormant epidermal stem cell niche contains two coexisting populations of stem cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. In dormant niches, the core molecular clock protein Bmal1 transcriptionally modulates the expression of stem cell regulatory genes, including modulators of Wnt and TGFb, to create two coexisting stem cell populations, one predisposed, and the other less prone, to activation. Unbalancing this equilibrium of epidermal stem cells, through conditional epidermal deletion of Bmal1, resulted in a long-term progressive accumulation of non-responsive stem cells, premature impairment of tissue self-renewal, and a significant reduction in the development of squamous cell carcinomas. Our results indicate that the molecular clock machinery fine-tunes the spatiotemporal behavior of epidermal stem cells within their niche, and that perturbation of this mechanism affects tissue homeostasis and the predisposition to neoplastic transformation. The goals of this study was to compare the transcriptome of epidermal stem cells according to their circadian rhythm phase. We isolated epidermal stem cells (bulge cells; alpha6bright/CD34+ population) from 19 days old Per1-Venus mice and separated them according to Venusbright (clock positive) and Venus dim (clock negative). The goals of this study was to compare the transcriptome of epidermal stem cells in which their circadian rhythm machinery has been perturbed by deleting the gene that encodes for Bmal1. We compared the transcriptomes of basal interfollicular epidermis cells (alpha6 integrin bright/CD34- cells) from the dorsal skin of 1 year old BmalKO mice and their respective control littermates. Each array corresponds to purified cells from approximately 5 mice. We profiled three samples of Venus bright and three of Venus dim epidermal stem cells. Each sample consisted of epidermal stem cells isolated from aproximately 20 mice (in order to obtain enough number of cells to perform high quality arrays). We profiled three WT samples and 3 KO samples. Each sample corresponds to basal interfollicular epidermis cells purified from 5 mice.
2011-12-08 | E-GEOD-27079 | biostudies-arrayexpress
Project description:Epidermal stem cells ensure that skin homeostasis is maintained. In murine skin, epidermal stem cells cluster at specific niches where, under steady-state conditions, they undergo cycles of dormancy and activation1. When cellular replenishment is required, epidermal stem cells egress from the niche and proliferate for a limited number of times to subsequently feed into the differentiated compartment1-3. However, only a subset of stem cells becomes active during each round of morphogenesis, suggesting that stem cells coexist in heterogeneous responsive states within the same niche. Using a circadian clock fluorescent reporter mouse model, we show that the dormant epidermal stem cell niche contains two coexisting populations of stem cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. In dormant niches, the core molecular clock protein Bmal1 transcriptionally modulates the expression of stem cell regulatory genes, including modulators of Wnt and TGFb, to create two coexisting stem cell populations, one predisposed, and the other less prone, to activation. Unbalancing this equilibrium of epidermal stem cells, through conditional epidermal deletion of Bmal1, resulted in a long-term progressive accumulation of non-responsive stem cells, premature impairment of tissue self-renewal, and a significant reduction in the development of squamous cell carcinomas. Our results indicate that the molecular clock machinery fine-tunes the spatiotemporal behavior of epidermal stem cells within their niche, and that perturbation of this mechanism affects tissue homeostasis and the predisposition to neoplastic transformation. The goals of this study was to compare the transcriptome of epidermal stem cells according to their circadian rhythm phase. We isolated epidermal stem cells (bulge cells; alpha6bright/CD34+ population) from 19 days old Per1-Venus mice and separated them according to Venusbright (clock positive) and Venus dim (clock negative). The goals of this study was to compare the transcriptome of epidermal stem cells in which their circadian rhythm machinery has been perturbed by deleting the gene that encodes for Bmal1. We compared the transcriptomes of basal interfollicular epidermis cells (alpha6 integrin bright/CD34- cells) from the dorsal skin of 1 year old BmalKO mice and their respective control littermates. Each array corresponds to purified cells from approximately 5 mice.
2011-12-08 | GSE27079 | GEO
Project description:To identify genes expressed predominantly in the ventral skin epidermal basal cells of pregnant mice, we performed DNA microarray analysis by using FACS-purified epidermal basal cells from ventral skin at 0 and 16 dpc, and dorsal skin at 16 dpc.
2016-08-30 | GSE86157 | GEO
Project description:MafB is a member of the Maf family of bZip transcription factor and plays important roles in the developmental processes of various tissues, as well as in cell-type specific gene expression. MafB is expressed in differentiating keratinocytes in mice and is transcriptionally up-regulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation is partially impaired and the cornified layer is thinner. To gain insights into more detailed molecular mechanisms of MafB regulation of epidermal development, we performed microarray analysis of mRNAs isolated from dorsal skin epidermis of MafB-/- and wild-type mice at E18.5. Epidermis was separated from dorsal skin tissues of E18.5 mouse embryos (MafB-/- and WT) by Dispase (Life Technologies) treatment. Total RNA was isolated using Trizol reagent (Life Technologies), purified using an RNeasy mini kit (Qiagen), and subjected to microarray analysis.
2015-11-26 | E-GEOD-75388 | biostudies-arrayexpress
Project description:Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes. To gain molecular understanding of the the hair cycle delay in Bmal mutant mice, we profiled the dorsal skin of Bmal knockout (-/-) and their heterozygous (+/-) littermates at P22. At P22, the skin samples are comparable because all the samples are in telogen just prior to the hair cycle delay was observed. Histological sections were used to classify each sample into specific stage of the hair growth cycle based on established morphological guidelines. RNA from each mouse dorsal skin were separately hybridized to an Affymetrix Mouse Gene 1.0 ST array.
2010-04-08 | E-GEOD-14006 | biostudies-arrayexpress
Project description:The aim of this study was to examine the effect of genetic disruption of the circadian clock on gene expression in the cortex across timepoints. Circadian clock protein regulate many critical aspects of cellular function, and Bmal1 knockout mice develop severe neuroinflammation, suggesting a role for circadian clock gene in brain homeostatic function. We compared brain-specific Bmal1 KO mice (Nestin-Cre;Bmal1(flox/flox) with Per1/2 double mutant mice, in order to assess the effects of deletion of the positive and negative limbs of the core clock. 11mo Cre-, NestinCre+/-;Bmal1(fx/fx), or Per1brdm,Per2brdm mice were entrained to 12h light:dark conditions with lights on at 6am for one month, then placed in constant darkness for 24 hours, after which mice were harvested at 6am (CT6) or 6pm (CT18), still in the dark. Mice were anesthetized in the dark, then perfused briefly with PBS+heparin. The brain was then quickly dissected on a cold surface, and the cerebral cortex flash frozen in liquid nitrogen. Cortex samples were mechanically dissociated with a Qiashredder device, then extracted with chloroform and diluted in 70% ethanol. RNA was extracted using Qiagen RNEasy kit according to manufacturers specifications. cDNAs were chemically labeled with Kreatech ULS RNA labeling kit (Kreatech Diagnostics) and Cy5-labeled cDNAs were hybridized to Agilent Mouse v2 4x44K microarrays (G4846A-026655).
2018-09-11 | E-MTAB-7151 | biostudies-arrayexpress
Project description:To help elucidate the metabolic changes in the skin that contribute to the obesity resistance and skin pathology in mice lacking Scd1, we performed microarray analysis of skin gene expression in male skin Scd1 knockout (SKO) and Scd1 flox/flox control (Lox) mice fed a standard rodent diet. We identified an extraordinary number of differentially expressed genes that support the previously documented histological observations of sebocyte atrophy, inflammation and epidermal hyperplasia in SKO mice. Additionally, transcript levels were reduced in skin of SKO mice for genes involved in fatty acid synthesis, elongation and desaturation, which may be attributed to decreased abundance of key transcription factors including SREBP1c, ChREBP and LXR?. Conversely, genes involved in cholesterol synthesis were increased, suggesting an imbalance between skin fatty acid and cholesterol synthesis. Unexpectedly, we observed a robust elevation in skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. These results highlight the importance of monounsaturated fatty acid synthesis for maintaining retinol homeostasis and point to disturbed retinol metabolism as a novel contributor to the Scd1 deficiency-induced skin pathology. We analyzed dorsal skin gene expression in non-fasted 8-9 week old male skin Scd1 knockout (SKO) mice (n=3) and Scd1flox/flox (Lox) control mice (n=3)on a C57BL/6J background using Affymetrix 430 2.0 microarrays.
2011-05-09 | E-GEOD-24243 | biostudies-arrayexpress
Project description:While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers. Whole skin was collected at ZT22. Where ZT number indicates the number of hours elapsed from when lights are switched on. ZT0 = lights on (6am). ZT12=lights off (6pm). Het mice designate a presence of one Bmal1 mutant allele and one wt allele. KO mice designate mice germline deleted for both copies of Bmal1 allele. Total RNA was purified from the skin of each biological littermate replicate.
2012-08-01 | E-GEOD-38624 | biostudies-arrayexpress
Project description:MafB is a member of the Maf family of bZip transcription factor and plays important roles in the developmental processes of various tissues, as well as in cell-type specific gene expression. MafB is expressed in differentiating keratinocytes in mice and is transcriptionally up-regulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation is partially impaired and the cornified layer is thinner. To gain insights into more detailed molecular mechanisms of MafB regulation of epidermal development, we performed microarray analysis of mRNAs isolated from dorsal skin epidermis of MafB-/- and wild-type mice at E18.5.
2015-11-26 | GSE75388 | GEO
Project description:Analysis of skin lesions from adult mice with epidermal conditional deletion of heterotrimeric G protein Galpha s in cytokeratin 14 positive cells, compared with control mouse skin. Epidermal Gnas ablation leads to skin defects, including basal cell carcinoma (BCC). Results provide insight into role of Galpha s in the regulation of stem cells from the skin. Changes in gene expression following Gnas deletion from the mouse epidermis were analyzed. Skin from four independent mice of each wild type (control) and Gnas epidermal knockout (Gnas eKO) were analyzed.
2014-06-28 | E-GEOD-58894 | biostudies-arrayexpress