Similar Datasets
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2022-11-01 | GSE201884 | GEO
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2023-04-05 | GSE202583 | GEO
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2022-11-01 | GSE202075 | GEO
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2022-11-01 | GSE202085 | GEO
Project description:Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice display delayed onset of first postnatal anagen, with increased DNA damage and diminished HFSC proliferation. Through transcriptomic and epigenetic analysis, we discover the formation of open chromatin regions near key cell cycle progression- and DNA damage repair genes in Irx5-/- HFSC. We also identify DNA damage repair factors BRCA1 and BARD1 as IRX5 downstream targets. Inhibition of FGF18 kinase signaling partially rescues the anagen delay in Irx5-/- mice, indicating that the Irx5-/- HFSC quiescent phenotype is in part due to failure to suppress Fgf18 expression. Our findings identify IRX5 as a required promoter of DNA damage repair in HFSC activation and hair cycle initiation.
2022-11-01 | GSE202086 | GEO
Project description:Hair follicles (HFs) maintain homeostasis through the hair cycles; therefore, disrupting the hair cycle may lead to hair loss. Our previous study showed that apoptosis-inducing factor (AIF) nuclear translocation and poly [ADP-ribose] polymerase 1 (PARP1) upregulation induced apoptosis in mouse hair follicles during the hair cycle transition from anagen to catagen. However, the mechanism underlying this phenomenon remains unclear. In this study, we found that intrinsic ROS levels increased during the hair follicle cycle transition from anagen to catagen, followed by abrupt DNA breaks and activation of homologous recombinant and nonhomologous end joining DNA repair, along with the enhancement of apoptosis. Mice in different stages of the hair cycle were sacrificed, and the dorsal skins were collected. The results of western blot and histological staining indicated that AIF-PARP1 plays a key role in HF apoptosis, but their role in the regulation of the HF cycle is not clear. Mice were treated with inhibitors from anagen to catagen: treatment with BMN 673, a PARP1 inhibitor, increased DNA breaks and activated the cytochrome c/caspase-3-mediated apoptotic pathway, accelerating HF regression. Ac-DEVD-CHO (Ac), a caspase-3 inhibitor, attenuated HF degeneration by upregulating PARP1 expression, suggesting a seesaw relationship between cytochrome c-caspase-3- and AIF-PARP1-mediated apoptosis, wherein PARP1 may be the fulcrum. In addition, macrophages were involved in regulating the hair cycle, and the rate of M1 macrophages around HFs increased during catagen, while more M2 macrophages were found during anagen and telogen. Our results indicate that intrinsic ROS drive HF cycle progression through DNA damage and repair, followed by apoptosis. Intrinsic ROS drive hair follicle cycle progression by modulating DNA damage and repair, and consecutively, hair follicle apoptosis and macrophage polarization work together to promote the hair follicle cycle.
| S-EPMC9315455 | biostudies-literature
Project description:Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.
| S-EPMC5657543 | biostudies-literature
Project description:The hair follicle is an ideal system to study stem cell specification and homeostasis due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft. The adult hair follicle stem cell niche consists of two distinct populations, the bulge and the more activation-prone secondary hair germ (HG). Hair follicle stem cells are set aside during early stages of morphogenesis. This process is known to depend on the Sox9 transcription factor, but otherwise the establishment of the hair follicle stem cell niche is poorly understood. Here, we show that that mutation of Foxi3, a Forkhead family transcription factor mutated in several hairless dog breeds, compromises stem cell specification. Further, loss of Foxi3 impedes hair follicle downgrowth and progression of the hair cycle. Genome-wide profiling revealed a number of downstream effectors of Foxi3 including transcription factors with a recognized function in hair follicle stem cells such as Lhx2, Runx1, and Nfatc1, suggesting that the Foxi3 mutant phenotype results from simultaneous downregulation of several stem cell signature genes. We show that Foxi3 displays a highly dynamic expression pattern during hair morphogenesis and cycling, and identify Foxi3 as a novel secondary HG marker. Absence of Foxi3 results in poor hair regeneration upon hair plucking, and a sparse fur phenotype in unperturbed mice that exacerbates with age, caused by impaired secondary HG activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. Stem Cells 2016;34:1896-1908.
| S-EPMC5287380 | biostudies-literature
Project description:It is known that LGR4 plays an important role in hair follicle (HF) development, but the impact of LGR4 on the hair cycle is still unclear. In this study, we have found that K14-Cre-mediated skin epithelia-specific deletion of Lgr4 results in delayed anagen entry during the physiological hair cycle and compromised HF regeneration upon transplantation. We show that, although Lgr4 deletion does not appear to affect the number of quiescent HF stem cells, it leads to reduced numbers of LGR5+ and actively proliferating stem cells in the HFs. Moreover, LGR4-deficient HFs show molecular changes consistent with decreased mTOR and Wnt signaling but upregulated BMP signaling. Importantly, the reactivation of the protein kinase B pathway by injecting the protein kinase B activator SC79 in Lgr4-/- mice can effectively reverse the hair cycle delay. Together, these data suggest that LGR4 promotes the normal hair cycle by activating HF stem cells and by influencing the activities of multiple signaling pathways that are known to regulate HF stem cells. Our study also implicates LGR4 as a potential target for treating hair disorder in the future.
| S-EPMC8507220 | biostudies-literature
Project description:Restoration of barrier-tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In response to skin injury, hair-follicle stem cells (HFSCs), normally poised for hair generation, are recruited to the site of injury and differentiate into cells that repair damaged epithelium. We used a SC fate-mapping approach to examine the contribution of regulatory T (Treg) cells to epidermal-barrier repair after injury. Depletion of Treg cells impaired skin-barrier regeneration and was associated with a Th17 inflammatory response and failed HFSC differentiation. In this setting, damaged epithelial cells preferentially expressed the neutrophil chemoattractant CXCL5, and blockade of CXCL5 or neutrophil depletion restored barrier function and SC differentiation after epidermal injury. Thus, Treg-cell regulation of localized inflammation enables HFSC differentiation and, thereby, skin-barrier regeneration, with implications for the maintenance and repair of other barrier tissues.
| S-EPMC6507428 | biostudies-literature