Obesity accelerates hair thinning in stem cell-centric converging mechanism
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ABSTRACT:
PROVIDER: PRJNA545462 | ENA |
REPOSITORIES: ENA
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Project description:Obesity accelerates hair thinning by stem cell-centric converging mechanism [RNA-seq]
| PRJNA715473 | ENA
Project description:Obesity, a worldwide epidemic, predisposes to many ageing-associated diseases, yet its exact impact on organ dysfunction is largely unknown. Hair follicles, mini-epithelial organs that grow hair, miniaturize by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs). Here, we report that obesity-induced stress such as by high-fat diet (HFD) feeding primarily targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days directs activated HFSCs toward epidermal keratinization by generating excessive reactive oxygen species yet retains HFSC pools in young mice. Integrative analysis with stem cell fate tracing, epigenetic analysis and reverse genetics revealed that further feeding of HFD subsequently induces lipid droplets and NF-κB activation within HFSCs via autocrine/paracrine IL1R signaling. Those integrated factors converge on the profound inhibition of Sonic hedgehog (Shh) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs from the skin surface and inducing hair follicle miniaturization and eventual hair loss. Conversely, Shh activation by transgenes or compounds rescues HFD-induced hair loss. These data collectively demonstrate that stem cell inflammageing induced by obesity robustly represses organ regeneration signals to accelerate the mini-organ miniaturization, and indicates suggests the importance of daily prevention of organ dysfunction.
2021-04-14 | GSE131958 | GEO
Project description:Obesity, a worldwide epidemic, predisposes to many ageing-associated diseases, yet its exact impact on organ dysfunction is largely unknown. Hair follicles, mini-epithelial organs that grow hair, miniaturize by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs). Here, we report that obesity-induced stress such as by high-fat diet (HFD) feeding primarily targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days directs activated HFSCs toward epidermal keratinization by generating excessive reactive oxygen species yet retains HFSC pools in young mice. Integrative analysis with stem cell fate tracing, epigenetic analysis and reverse genetics revealed that further feeding of HFD subsequently induces lipid droplets and NF-B activation within HFSCs via autocrine/paracrine IL1R signaling. Those integrated factors converge on the profound inhibition of Sonic hedgehog (Shh) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs through their aberrant differentiation and inducing hair follicle miniaturization and eventual hair loss. Conversely, Shh activation by transgenes or compounds rescues HFD-induced hair loss. These data collectively demonstrate that stem cell inflammageing induced by obesity robustly represses organ regeneration signals to accelerate the mini-organ miniaturization, and suggests the importance of daily prevention of organ dysfunction.
2021-04-14 | GSE169173 | GEO
Project description:Obesity is a worldwide epidemic that predisposes individuals to many age-associated diseases, but its exact effects on organ dysfunction are largely unknown1. Hair follicles-mini-epithelial organs that grow hair-are miniaturized by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs)2. Here we report that obesity-induced stress, such as that induced by a high-fat diet (HFD), targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days in young mice directed activated HFSCs towards epidermal keratinization by generating excess reactive oxygen species, but did not reduce the pool of HFSCs. Integrative analysis using stem cell fate tracing, epigenetics and reverse genetics showed that further feeding with an HFD subsequently induced lipid droplets and NF-κB activation within HFSCs via autocrine and/or paracrine IL-1R signalling. These integrated factors converge on the marked inhibition of Sonic hedgehog (SHH) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs through their aberrant differentiation and inducing hair follicle miniaturization and eventual hair loss. Conversely, transgenic or pharmacological activation of SHH rescued HFD-induced hair loss. These data collectively demonstrate that stem cell inflammatory signals induced by obesity robustly represses organ regeneration signals to accelerate the miniaturization of mini-organs, and suggests the importance of daily prevention of organ dysfunction.
| S-EPMC9600322 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE16432: MSI2 regulates hematopoiesis and accelerates leukemogenesis GSE22773: Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (LK and MS12-inducible) GSE22774: Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (LSK and LK) GSE22775: Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (Leukemia cell lines) Refer to individual Series
2010-07-21 | E-GEOD-22778 | biostudies-arrayexpress
Project description:Primary outcome(s): Comparison of the gene expression profile in hair follicle between cancer patients and healthy volunteer
| 2628246 | ecrin-mdr-crc
Project description:This SuperSeries is composed of the following subset Series: GSE28948: TMPRSS2-ERG, HDACs and EZH2 are involved in an AR-centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (gene expression data) GSE28950: TMPRSS2-ERG, HDACs and EZH2 are involved in an AR-centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (ChIP-Seq data) GSE35540: TMPRSS2-ERG, HDACs and EZH2 are involved in an AR centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (gene expression after ERG KD) Refer to individual Series
2012-04-26 | E-GEOD-28951 | biostudies-arrayexpress
Project description:GPR54, or KiSS-1R (Kisspeptin receptor), is key in puberty initiation and tumor metastasis prevention, but its role on hair follicles remains unclear. Our study shows that Gpr54 knockout (KO) accelerates hair cycle, synchronized hair regeneration and transplanted hair growth in mice. In Gpr54 KO mice, DPC (dermal papilla cell) activity is enhanced, with elevated expression of Wnts, VEGF, and IGF-1, which stimulate HFSCs. Gpr54 deletion also raises the number of CD34+ and Lgr5+ HFSCs. The Gpr54 inhibitor, kisspeptin234, promotes hair shaft growth in cultured mouse hair follicles and boosts synchronized hair regeneration in vivo. Mechanistically, Gpr54 deletion suppresses NFATC3 expression in DPCs and HFSCs, and decreases levels of SFRP1, a Wnt inhibitor. It also activates the Wnt/β-catenin pathway, promoting β-catenin nuclear localization and upregulating target genes such as Lef1 and ALP. Our findings suggest that Gpr54 deletion may accelerate the hair cycle and promote hair regeneration in mice by regulating the NAFTc3-SFRP1-Wnt signaling pathway. These findings suggest that Gpr54 could be a possible target for future hair loss treatments.
| S-SCDT-10_1038-S44319-024-00327-Y | biostudies-other
Project description:Telogen (resting phase) hair follicles are more radioresistant than anagen (growth phase) ones. Irradiation of BALB/c mice in the anagen phase with γ-rays at 6 Gy induced hair follicle dystrophy, whereas irradiation in the telogen phase induced the arrest of hair follicle elongation without any dystrophy after post-irradiation depilation. In contrast, FGF18 was highly expressed in the telogen hair follicles to maintain the telogen phase and also the quiescence of hair follicle stem cells. Therefore, the inhibition of FGF receptor signaling at telogen induced the dystrophy after post-irradiation depilation. In addition, the administration of recombinant FGF18 suppressed cell proliferation in the hair follicles and enhanced the repair of radiation-induced DNA damage, so FGF18 protected the anagen hair follicles against radiation damage to enhance hair regeneration. Moreover, FGF18 reduced the expression of cyclin B1 and cdc2 in the skin and FGF18 signaling induced G2/M arrest in the keratinocyte cell line HaCaT, although no obvious change of the expression of DNA repair genes was detected by DNA microarray analysis. These findings suggest that FGF18 signaling for the hair cycle resting phase causes radioresistance in telogen hair follicles by arresting the proliferation of hair follicle cells.
2017-06-03 | GSE69501 | GEO
Project description:Hair shafts are formed by terminal differentiation of hair keratinocytes (trichocytes) in which keratins and keratin-associated proteins accumulate and undergo cross-linking. Here we tested the hypothesis that maturation of the hair shaft also involves the coordinated degradation of other proteins and, specifically, that this degradation is mediated by autophagy. To this end, we deleted the non-redundant autophagy regulator Atg7 in keratinocytes of the epidermis and skin appendages, including hair, and determined the proteome of hair shafts from fully autophagy-competent and epithelial autophagy-deficient mice. The abrogation of autophagy led to significantly increased abundance of proteins regulating house-keeping functions of the cell and a decrease of cytoskeletal proteins. Translation factors, tRNA-ligases, ribosomal proteins and the components of proteasomes were particularly elevated in the absence of autophagy, indicating a central role of autophagy in regulating multiple steps of protein turnover in hair keratinocytes. These results demonstrate that hair keratinocytes depend on autophagy for establishing the mature protein composition of hair.
2023-01-17 | MSV000091072 | MassIVE