Ontology highlight
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PROVIDER: PRJNA1250787 | ENA |
REPOSITORIES: ENA
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Project description:The extracellular matrix (ECM) plays a crucial role in building the extracellular environment and translating extracellular information into biochemical signals that sustain organ functions. Fibulin-5 is a multifunctional ECM protein essential for the formation of elastic fibers and the regulation of cellular functions through integrin binding. Fibulin-5 expression decreases with aging in human skin; however, its functional significance remains unknown. To address the roles of fibulin-5 in regulating epidermal stem cells during skin aging, Fbln5 knockout mice were examined for changes in their cellular and molecular phenotypes. Loss of Fbln5 in mice results in early impairments of epidermal stem cell properties, similar to the chronological aging of the skin. Fibulin-5 deficiency results in the suppression of integrins and other cell junctional molecules, leading to the inactivation of YAP signaling in epidermal stem cells. The reduced YAP signal is associated with the down-regulation of the fast-cycling epidermal stem cell marker, SLC1A3, in human skin and primary keratinocytes. These findings underscore the important role of fibulin-5 in governing the balance of epidermal stem cell populations during skin aging via crosstalk between the extracellular environment and intracellular signaling.
2025-05-01 | GSE295189 | GEO
Project description:This study was performed to compare the transcriptome of epidermal stem cells in young (2 months old) and middle aged (1 year old) fibulin 7 wild type (WT) compared to fibulin 7 knockout (KO) mice. Fbln7 gene was an ECM gene significantly upregulated in aging fast-cycling stem cells and this RNA-sequencing was done to investigate the role of Fbln7 in aging epidermal stem cells. Data indicates differences in gene expressions occuring between WT and KO at 1 year old but not at 2 months old, suggesting an age dependent role of fibulin 7. At 1 year old, other matrix-related and remodelling genes were affected, together with inflammatory responses of stem cells and lineage fate abberations, as in the case of 2 years old fast-cycling epidermal stem cells.
2022-10-01 | GSE185086 | GEO
Project description:Millions suffer from skin diseases. Functional epidermal stem cells are needed in skin therapy or drug screening in vitro. We obtained functional epidermal stem cells with intact stemness and cell junctions by treating them with wnt3a. Moreover, epidermal stem cell-derived exosomes were useful in epidermal development. Finally, functional epidermal 3D organoids with polarity were cultured using wnt3a and the supernatant derived from epidermal stem cells and fresh medium in a 1:1 ratio. These results provide novel directions for the improvement of skin organoids and their potential in clinical application.
2020-07-14 | PXD020351 |
Project description:This study was performed to compare transcriptomic changes in the heterogeneous mouse skin epidermal stem cells and hair follicle stem cells (HFSC) populations during chronological aging. Slow-cycling stem cells (label retaining cells, LRCs), fast-cycling stem cells (non-label retaining cells, nLRCs) and hair follicle stem cells express unique gene signatures in young age (2 months old) and have independent stem cell identities. The changes in aging stem cells lineage identities have been a topic of discussion and here we examined if distinct stem cells cycling speed affects their aging process by comparing the transcriptomes of slow-and fast-cycling epidermal stem cells. Our data indicates the loss of unique stem cell identities in aging slow or fast-cycling epidermal stem cells or HFSC at 2 years of age with intermediary effects seen at 1.5 year old.
2022-10-01 | GSE185087 | GEO
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:The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner
| PRJNA601160 | ENA
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: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
Project description:Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been more recently linked to impaired skin function in old humans. Understanding of these metabolic adaptations in aged skin are of special interest, because topical treatments could reverse age-dependent metabolic changes of human skin in vivo to affect age associated skin disorders. Results: We investigated the global metabolic adaptions in human skin during aging with a combined transcriptomic and metabolomic approach applied to epidermal tissue samples of young and old human volunteers. Our analysis confirmed known age-dependent metabolic alterations, e.g. reduction of coenzyme Q10 levels, and also revealed novel age effects that are seemingly important for skin maintenance. Integration of donor-matched transcriptome and metabolome data highlighted transcriptionally-driven alterations of metabolism during aging such as altered activity in upper glycolysis and glycerolipid biosynthesis or decreased protein and polyamine biosynthesis. Together, we identified several age-dependent metabolic alterations that might affect cellular signaling, epidermal barrier function, and skin structure and morphology. Conclusion: Our study provides a global resource on the metabolic adaptations and its transcriptional regulation during aging of human skin. Thus, it represents a first step towards an understanding of the impact of metabolism on impaired skin function in aged humans and therefore will potentially lead to improved treatments of age related skin disorders
2017-01-20 | GSE85358 | GEO