Similar Datasets
Project description:The maintenance of tissue homeostasis in steady state or under stress is dependent on the proper communication between tissue-resident stem cells (SCs) and immune cells in their microenvironment or “niche”. In addition to promoting immune tolerance, regulatory T cells (Tregs) have recently emerged as a critical component of stem cell niche in the hair follicle (HF), injured muscle, bone marrow and intestine to support stem cell differentiation. How Treg cells sense the dynamic signals in the niche environment and communicate with stem cells during tissue regeneration is largely unknown. Here, by using HF as a model, we uncover a hitherto unrecognized function of glucocorticoid receptor (GR) signaling pathway in skin-resident Treg cells to facilitate hair follicle stem cell (HFSC) activation and HF regeneration. Ablation of GR signaling in Tregs blocked HFSCs activation and proliferation after hair depilation and during the natural hair growth cycle. Mechanistically, GR signaling induces skin-resident Tregs to produce TGF-b3, which activates Smad2/3 in HFSCs and promotes HFSC proliferation and hair growth. Our study identifies a novel crosstalk between skin-resident Tregs and HFSCs mediated by the GR/TGF-b3 axis, highlighting a new avenue to manipulate Tregs to support tissue regeneration.
2022-05-02 | GSE183805 | GEO
Project description:The maintenance of tissue homeostasis in steady state or under stress is dependent on the proper communication between tissue-resident stem cells (SCs) and immune cells in their microenvironment or “niche”. In addition to promoting immune tolerance, regulatory T cells (Tregs) have recently emerged as a critical component of stem cell niche in the hair follicle (HF), injured muscle, bone marrow and intestine to support stem cell differentiation. How Treg cells sense the dynamic signals in the niche environment and communicate with stem cells during tissue regeneration is largely unknown. Here, by using HF as a model, we uncover a hitherto unrecognized function of glucocorticoid receptor (GR) signaling pathway in skin-resident Treg cells to facilitate hair follicle stem cell (HFSC) activation and HF regeneration. Ablation of GR signaling in Tregs blocked HFSCs activation and proliferation after hair depilation and during the natural hair growth cycle. Mechanistically, GR signaling induces skin-resident Tregs to produce TGF-b3, which activates Smad2/3 in HFSCs and promotes HFSC proliferation and hair growth. Our study identifies a novel crosstalk between skin-resident Tregs and HFSCs mediated by the GR/TGF-b3 axis, highlighting a new avenue to manipulate Tregs to support tissue regeneration.
2022-05-02 | GSE183804 | GEO
Project description:Regulatory T cells in skin promote hair follicle stem cell activation and hair growth through glucocorticoid signaling
| PRJNA762035 | ENA
Project description:Regulatory T cells in skin promote hair follicle stem cell activation and hair growth through glucocorticoid signaling (RNA-Seq)
| PRJNA762044 | ENA
Project description:Regulatory T cells in skin promote hair follicle stem cell activation and hair growth through glucocorticoid signaling (ChIP-Seq)
| PRJNA762045 | ENA
Project description:Maintenance of tissue homeostasis is dependent on the communication between stem cells and supporting cells in the same niche. Regulatory T cells (Treg cells) are emerging as a critical component of the stem-cell niche for supporting their differentiation. How Treg cells sense dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, by using hair follicles (HFs) to study Treg cell-stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in instructing skin-resident Treg cells to facilitate HF stem-cell (HFSC) activation and HF regeneration. Ablation of the glucocorticoid receptor (GR) in Treg cells blocks hair regeneration without affecting immune homeostasis. Mechanistically, GR and Foxp3 cooperate in Treg cells to induce transforming growth factor β3 (TGF-β3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation. The present study identifies crosstalk between Treg cells and HFSCs mediated by the GR-TGF-β3 axis, highlighting a possible means of manipulating Treg cells to support tissue regeneration.
| S-EPMC9283297 | biostudies-literature
Project description:It is well recognized that regulating the hair follicle cycle in association with Wnt signaling is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether selected herbal medicines processed by decoction and fermentation promote hair growth by upregulating the number and size of hair follicles and Wnt signaling, including activation of β-catenin and Akt in telogen-synchronized C57BL/6N mice. The results revealed that the fermented extract after decoction (FDE) more effectively promoted hair growth than that of a nonfermented extract (DE). Notably, FDE effectively enhanced formation of hair follicles with clearer differentiation between the inner and outer root sheath, which is observed during the anagen phase. Mechanistic evidence was found for increased β-catenin and Akt phosphorylation levels in dorsal skin tissue along with elevated expression of hair regrowth-related genes, such as Wnt3/10a/10b, Lef1, and fibroblast growth factor 7. In conclusion, our findings suggest that FDE plays an important role in regulating the hair cycle by increasing expression of hair regrowth-related genes and activating downstream Wnt signaling targets.
| S-EPMC4823488 | biostudies-literature
Project description:The polarity of mouse hair follicles is controlled by the Frizzled (Fzd) receptors and other membrane planar cell polarity (PCP) proteins. Whether Wnt proteins can act as PCP ligands in the skin remains unknown. Here, we show that overexpression of Wnt5a in the posterior part of mouse embryos causes a local disruption of hair follicle orientation. The misoriented hair follicle phenotype in Wnt5a overexpressing mice can be rescued by a heterozygous loss of Fzd6, suggesting Wnt5a is likely to signal through Fzd6. Although the membrane distribution of PCP proteins seems unaffected by Wnt5a overexpression, transcriptional profiling analyses identify a set of genes as potential targets of the skin polarization program controlled by Wnt5a/Fzd6 signaling. Surprisingly, deletion of Wnt5a globally or in the posterior part of the mouse embryos does not affect hair follicle orientation. We show that many other Wnts are highly expressed in the developing skin. They can activate the Fzd6 signaling pathway in vitro and may act together with Wnt5a to regulate the Fzd6-mediated skin polarization. Our experiments demonstrate for the first time that Wnt5a can function as an orienting cue for mouse skin PCP.
| S-EPMC9845745 | biostudies-literature
Project description:BackgroundAccumulating evidence shows that mesenchymal stem cell-derived extracellular vesicles (EVs) hold great promise to promote hair growth. However, large-scale production of EVs is still a challenge. Recently, exosome-mimetic nanovesicles (NV) prepared by extruding cells have emerged as an alternative strategy for clinical-scale production. Here, ReNcell VM (ReN) cells, a neural progenitor cell line was serially extruded to produce NV.ResultsReN-NV were found to promote dermal papilla cell (DPC) proliferation. In addition, in a mouse model of depilation-induced hair regeneration, ReN-NV were injected subcutaneously, resulting in an acceleration of hair follicle (HF) cycling transition at the site. The underlying mechanism was indicated to be the activation of Wnt/β-catenin signaling pathway. Furthermore, miR-100 was revealed to be abundant in ReN-NV and significantly up-regulated in DPCs receiving ReN-NV treatment. miR-100 inhibition verified its important role in ReN-NV-induced β-catenin signaling activation.ConclusionThese results provide an alternative agent to EVs and suggest a strategy for hair growth therapy.
| S-EPMC7802142 | biostudies-literature
Project description:Mammalian injury responses are predominantly characterized by fibrosis and scarring rather than functional regeneration. This limited regenerative capacity in mammals could reflect a loss of proregeneration programs or active suppression by genes functioning akin to tumor suppressors. To uncover programs governing regeneration in mammals, we screened transcripts in human participants following laser rejuvenation treatment and compared them with mice with enhanced wound-induced hair neogenesis (WIHN), a rare example of mammalian organogenesis. We found that Rnasel-/- mice exhibit an increased regenerative capacity, with elevated WIHN through enhanced IL-36α. Consistent with RNase L's known role to stimulate caspase-1, we found that pharmacologic inhibition of caspases promoted regeneration in an IL-36-dependent manner in multiple epithelial tissues. We identified a negative feedback loop, where RNase L-activated caspase-1 restrains the proregenerative dsRNA-TLR3 signaling cascade through the cleavage of toll-like adaptor protein TRIF. Through integrated single-cell RNA-seq and spatial transcriptomic profiling, we confirmed OAS & IL-36 genes to be highly expressed at the site of wounding and elevated in Rnasel-/- mouse wounds. This work suggests that RNase L functions as a regeneration repressor gene, in a functional trade off that tempers immune hyperactivation during viral infection at the cost of inhibiting regeneration.
| S-EPMC11910212 | biostudies-literature