Fig 1: Hmmr+ FBs interact with DP via the Ncam1–Fgfr1 pathway to promote hair regeneration in skin organoid models. (A) Left: IF staining shows the effects of Ncam1 and Fgfr1 inhibitor treatments on the expression of Bmp4, β-catenin, Lef1, and PCNA in mouse skin organoid models. Right: Quantification of hair regeneration in nude mice after transplantation following inhibitor treatment. Scale bar, 25 μm. (B) Schematic illustrating the mechanism by which Hmmr promotes hair follicle regeneration: During hair follicle regeneration, the upper dermis (effector) increases the viscoelasticity of the ECM by regulating HA synthesis and Eln expression. This change is sensed by Hmmr+ cells (sensor), leading to Hmmr activation. Subsequently, via the Ncam1–Fgfr1 signaling pathway, these cells interact with the DP cells (executor), ultimately promoting hair follicle regeneration. Mean ± SEM (n = 3). One-way ANOVA with Tukey’s post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001.
Fig 2: Mechanical crosstalk between fibroblasts and ECM directs follicle regeneration. (A) Representative loading–unloading curves and corresponding loss coefficients of ECM in HMMR+ fibroblast regions at telogen and early anagen stages detected by atomic force microscopy (AFM). (B) AFM-based quantitative analysis of ECM adhesion force in HMMR+ fibroblast regions at telogen and early anagen stages (n = 16; P < 0.05, **P < 0.01, ***P < 0.001). (C) Representative loading–unloading curves and corresponding loss coefficients of ECM in HMMR+ fibroblast regions following subcutaneous Eln treatment detected by AFM. (D) AFM-based quantitative analysis of ECM adhesion force in HMMR+ fibroblast regions following subcutaneous Eln treatment (n = 16; P < 0.05, **P < 0.01, ***P < 0.001). (E) IF staining demonstrating the effect of subcutaneous Eln injection on the expression of Bmp4, β-catenin, Lef1, and PCNA (PPD4). Scale bar, 25 μm. (F and G) IF staining reveals the effects of subcutaneous Eln and HA injections on Hmmr expression. Scale bar, 50 μm. (H and I) Gene scoring analysis indicates that HA synthesis and Eln expression are predominantly localized in the FB1 cell subpopulation. (J) CellChat analysis compares the interaction numbers between dermal cell subpopulations and FB1 in telogen and early anagen hair follicles. (K) Information flow of interactions between dermal cell subpopulations and FB1 in telogen and early anagen hair follicles. (L) Bubble plot illustrates FGF signaling pathways in DP–FB1 interactions. Mean ± SEM (n = 3). Unpaired 2-tailed t test. *P < 0.05, **P < 0.01, ***P < 0.001.
Fig 3: Regulation of hair regeneration by increased ECM viscoelasticity in mouse skin organoids. (A) Masson staining showing collagen distribution in the ECM of hair follicles at telogen and anagen phases in young and old mouse. Scale bar, 50 μm. (B) Masson and Herovici staining showing the effect of subcutaneous injection of HA and Eln on collagen regeneration in the skin. Scale bar, 50 μm. (C and D) IF staining highlighting the impact of subcutaneous injection of HA and Eln on the expression of Bmp4, β-catenin, Lef1, and PCNA. Scale bar, 50 μm. (E) Left: IF staining showing the effects of HA and Eln on the expression of Bmp4, β-catenin, Lef1, and PCNA in the mouse skin organoid model. Right: Quantitative comparison of hair regeneration after transplantation into nude mice between HA/Eln treatment groups and the control group. Scale bar, 25 μm. Mean ± SEM (n = 3). Unpaired 2-tailed t test or one-way ANOVA with Tukey’s post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001.
Supplier Page from Fine Biotech Co., Ltd. for Recombinant Human ELN