Coordinated hedgehog signaling induces new hair follicles in adult skin.
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ABSTRACT:
SUBMITTER: Sun X
PROVIDER: S-EPMC7077985 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with the interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12, which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell-autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing IL-17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function.
| S-EPMC11317994 | biostudies-literature
Project description:BackgroundCD1d belongs to a family of antigen presenting molecules that are structurally and distantly related to the classic major histocompatibility complex class I (MHC I) proteins. However, unlike MHC I molecules, which bind protein antigens, CD1d binds to lipid and glycolipid antigens. CD1d is expressed by cells of lymphoid and myeloid origin, and by cells outside of the lymphoid and myeloid lineages, such as human keratinocytes of psoriatic skin.AimsTo investigate whether CD1d is also expressed in sun exposed skin and in the immuno-privileged anagen hair follicle.Materials/methodsCD1d immunoreactivity was studied in human scalp skin and hair follicles of healthy women in situ by immunofluorescent and light microscopic immunohistology. Skin biopsies were obtained from normal human scalp containing mainly anagen VI hair follicles from women (age, 53-57 years) undergoing elective plastic surgery.ResultsCD1d showed strong immunostaining in human scalp skin epidermis, pilosebaceous units, and eccrine glands. In the epidermis, CD1d was strongly expressed by basal and granular keratinocytes. In hair follicles, CD1d was expressed in the epithelial compartment and showed hair cycle related alterations, with an increase in the anagen and a reduction in the catagen and telogen phases.ConclusionsThese results suggest that CD1d plays a role in human scalp skin immunology and protection against lipid antigen rich infectious microbes. They also raise the question of whether keratinocytes of the immuno-privileged anagen hair follicle can present lipid antigens to natural killer T cells. These data could help provide new strategies for the manipulation of hair related disorders.
| S-EPMC1770800 | biostudies-literature
Project description:Background: Hair follicles play an essential role in the growth of hair. Epigallocatechin-3-gallate (EGCG), a catechin polyphenol in green tea, has various bioactivities. The present study aims to evaluate the effect of EGCG on the growth of mink hair follicles and investigate the possible molecular mechanisms. Methods: The length of hair follicles was recorded up to 6 days in presence of 0.1-5 ?M EGCG. Primary dermal papilla cells (DPCs) and outer root sheath cells (ORSCs) were treated with 0.25-4 ?M EGCG, and their growth was evaluated by MTT assay and cell cycle detection. The levels of key molecules in sonic hedgehog (Shh) and protein kinase B (AKT) signaling pathways were further assessed by quantitative real-time PCR, western blot and immunofluorescence. To determine the involvement of Shh and AKT pathways in EGCG-mediated growth-promotion of ORSCs and DPCs, Shh pathway inhibitors cyclopamine and GANT61 or AKT pathway inhibitor LY294002 were employed, and then cell proliferation and cell cycle were analyzed. Results: Data from ex vivo culture showed that, in presence of 0.5-2.5 ?M EGCG, the growth of mink hair follicles was promoted. In vitro, the proliferation of DPCs and ORSCs was enhanced by 0.5-4 ?M EGCG treatment. More cells entered S phase upon treatment of EGCG, accompanied with upregulation of cyclin D1 and cyclin E1. Furthermore, when exposed to EGCG, the Shh and AKT signaling pathways were activated in both hair follicles and primary DPCs and ORSCs. Inhibiting either of these two pathways partly reversed the effect of EGCG on proliferation and cell cycle of DPCs and ORSCs. Conclusion: EGCG promotes the growth of mink hair follicles at concentrations of 0.5-2.5 ?M. This growth-promoting effect of EGCG may be associated with the increased proliferation of DPCs and ORSCs through activating Shh and AKT signaling pathways.
| S-EPMC6028712 | biostudies-literature
Project description:Growth and regeneration of one tissue within an organ compels accommodative changes in the surrounding tissues. However, the molecular nature and operating logic governing these concurrent changes remain poorly defined. The dermal adipose layer expands concomitantly with hair follicle downgrowth, providing a paradigm for studying coordinated changes of surrounding lineages with a regenerating tissue. Here, we discover that hair follicle transit-amplifying cells (HF-TACs) play an essential role in orchestrating dermal adipogenesis through secreting Sonic Hedgehog (SHH). Depletion of Shh from HF-TACs abrogates both dermal adipogenesis and hair follicle growth. Using cell type-specific deletion of Smo, a gene required in SHH-receiving cells, we found that SHH does not act on hair follicles, adipocytes, endothelial cells, and hematopoietic cells for adipogenesis. Instead, SHH acts directly on adipocyte precursors, promoting their proliferation and their expression of a key adipogenic gene, peroxisome proliferator-activated receptor γ (Pparg), to induce dermal adipogenesis. Our study therefore uncovers a critical role for TACs in orchestrating the generation of both their own progeny and a neighboring lineage to achieve concomitant tissue production across lineages.
| S-EPMC5110998 | biostudies-literature
Project description:We generated KA mutant mice (Krt14-CreERT + ABCA12-flox/flox) and controls (ABCA12-flox/flox) that enabled us to assess the effects of deleting a critical barrier gene, ABCA12, in the skin epidermis following tamoxifen treatment. These studies identified numerous differentially expressed genes (DEGs) upon barrier disruption/ABCA12 deletion, including compensatory upregulation of genes involved with epidermal differentiation and barrier function. Overall, this data-set provides a global view of molecular changes that occur in adult mouse skin following barrier perturbation.
2024-05-20 | GSE254889 | GEO
Project description:The composition of the skin microbiota varies widely among individuals when sampled at the same body site. A key question is which molecular factors determine strain-level variability within sub-ecosystems of the skin microbiota. Here, we used a genomics-guided approach to identify an antibacterial biosynthetic gene cluster in Cutibacterium acnes (formerly Propionibacterium acnes), a human skin commensal bacterium that is widely distributed across individuals and skin sites. Experimental characterization of this biosynthetic gene cluster resulted in identification of a new thiopeptide antibiotic, cutimycin. Analysis of individual human skin hair follicles revealed that cutimycin contributed to the ecology of the skin hair follicle microbiota and helped to reduce colonization of skin hair follicles by Staphylococcus species.
| S-EPMC8478231 | biostudies-literature
Project description:PURPOSE:Telogen (resting phase) hair follicles (HFs) are more radioresistant than their anagen (growth phase) counterparts. Fibroblast growth factor (FGF) 18 is strongly expressed in telogen HFs to maintain the telogen phase, whereas several other FGFs exert radioprotective effects; however, the role of FGF18 in the radioresistance of HFs remains unknown. This study focused on clarifying the role of FGF18 in the radioresistance of telogen HFs and its potential as a radioprotector. METHODS AND MATERIALS:BALB/c mice with telogen or plucking-induced anagen HFs were exposed to total body irradiation with ?-rays at 4 to 12 Gy after intraperitoneal treatment with FGF18 or an FGF receptor inhibitor. A time course analysis was performed histologically and hair growth was observed 14 or 15 days after depilation. Skin specimens were analyzed by DNA microarrays and Western blotting. RESULTS:Telogen irradiation at 6 Gy resulted in transient cell growth arrest, leading to successful hair growth, whereas anagen irradiation failed to promote hair growth. Telogen irradiation did not induce apoptosis in HFs or reduce HF stem cells, whereas anagen irradiation induced apoptosis and reduced stem cell numbers. The Inhibition of FGF receptor signaling during the telogen phase promoted HF cell proliferation; however, hair failed to grow after irradiation. In contrast, recombinant FGF18 induced transient cell growth arrest after anagen irradiation with enhanced DNA repair, leading to the inhibition of apoptosis, maintenance of HF stem cells, and successful hair growth. Moreover, FGF18 reduced the expression levels of genes promoting G2/M transition as well as the protein expression levels of cyclin B1 and cdc2 in skin, and induced G2/M arrest in the keratinocyte cell line HaCaT. CONCLUSIONS:These results suggest that FGF18 signaling mediates radioresistance in telogen HFs by arresting the cell cycle, and that FGF18 has potential as a radioprotector for radiation-induced alopecia.
| S-EPMC5514016 | biostudies-literature
Project description:The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for activating SCs during the adult hair cycle, but the signal exchange between niche and SC precursors/transit amplifying progenitor cells (TACs) that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs and the DP niche express a plethora of known and novel ligands and receptors. Signaling interaction network analysis reveals a birds-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth.
2016-03-17 | GSE77197 | GEO
Project description:Hair follicles modulate skin barrier function
| PRJNA1072231 | ENA
Project description:Skin and hair follicle morphogenesis and homeostasis require the integration of multiple signaling pathways, including Hedgehog (Hh) and Wingless (Wnt), and oriented cell divisions, all of which have been associated with primary cilia. Although studies have shown that disrupting dermal cilia causes follicular arrest and attenuated Hh signaling, little is known about the role of epidermal cilia. Here, epidermal cilia function was analyzed using conditional alleles of the ciliogenic genes Ift88 and Kif3a. At birth, epidermal cilia mutants appeared normal, but developed basaloid hyperplasia and ingrowths into the dermis of the ventrum with age. In addition, follicles in the tail were disorganized and had excess sebaceous gland lobules. Epidermal cilia mutants displayed fewer long-term label-retaining cells, suggesting altered stem cell homeostasis. Abnormal proliferation and differentiation were evident from lineage-tracing studies and showed an expansion of follicular cells into the interfollicular epidermis, as is seen during wound repair. These phenotypes were not associated with changes in canonical Wnt activity or oriented cell division. However, nuclear accumulation of the ?Np63 transcription factor, which is involved in stratification, keratinocyte differentiation and wound repair, was increased, whereas the Hh pathway was repressed. Intriguingly, the phenotypes were not typical of those associated with loss of Hh signaling but exhibited similarities with those of mice in which ?Np63 is overexpressed in the epidermis. Collectively, these data indicate that epidermal primary cilia may function in stress responses and epidermal homeostasis involving pathways other than those typically associated with primary cilia.
| S-EPMC3074444 | biostudies-literature