Project description:In order to identify genes that correlate with efficacy in clinical trials, titled Autologous cell–based therapy for male and female pattern hair loss using dermal sheath cup cells, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish efficacy. RNA was extracted from each DSC-cells that was used in the clinical trial, and gene expression profiling by microarrays was performed. DSC cells derived from representative 8 IDs of highly effective and less effecgive group were analyzed. Signature was identified that distinguished between highly and less effective IDs.
Project description:The dermal sheath cup is the peribulbar component of the hair follicle dermal sheath, and has hair inductive potential similar to the dermal papilla. To characterize it in comparison with other mesenchymal follicle tissuesparts, we performed gene expression profiling of intact dermal sheath cups, which were separated from hair follicles by microdissection. Gene expression profiles of the dermal sheath cup, dermal papilla and upper dermal sheath were compared. We identified a dermal sheath cup signature composed of 32 upregulated genes, which included extracellular matrix components and BMP binding mollecules, while dermal papilla signature included a number of dermal papilla signature genes which had already reported. Analyses of upstream regulators showed that TGF- b1 is a putative regulator of these genes. These results suggest some of molecular mechanism that contributes to human dermal sheath cup properties, which could be useful for hair follicle bioengineering.
Project description:Autologous cell-based therapy using dermal sheath cup (DSC) cell is a new approach for male and female pattern hair loss. While its efficacy was recently reported, the mechanism of action remains unclear. Furthermore, the differences in treatment response require clarification. First, we used multivariate analysis to categorize two groups of individuals: patients in which therapy showed high efficacy (HE group) and patients in which therapy showed low efficacy (LE group). Then We analyzed the differences in gene expression between DSC cells from the HE and LE groups by single-cel transcriptome.
Project description:Much is still unknown about the molecular regulatory networks which govern the dermal papilla’s (DP) ability to induce hair follicle regeneration, a capacity which gradually decreases with age. DP and dermal sheath cup (DSC) cells from mature, anagen phase, hair follicles were manually microdissected from fresh frozen sections of 16-18 week human fetal scalp and 30-60 year old adult male scalp. Interfollicular dermal (IFD) fibroblasts were harvested for comparison. RNA-seq libraries from each cell population were prepared with Nugen’s Ovation RNA-Seq and Ultralow Library systems, sequenced to approximately 100 million total reads. A set of 121 genes was identified as significantly upregulated in fetal DP cells, as compared to both fetal DSC and IFD populations. Wnt/β-catenin, Shh, FGF, BMP, and Notch signaling pathways were significantly enriched among those genes differentially expressed between fetal and adult DP cells. Among them, Spondin-1, a Wnt agonist, was chosen for verification and can rescue hair follicle regeneration in skin reconstitution assays using cells from adult mice. Additionally, twenty-nine transcription factors were significantly upregulated in fetal DP compared to adult DP cells. Of those, seven transcription factor binding motifs were significantly enriched in the candidate promoter regions of differentially expressed genes between fetal and adult DP cells, suggesting a combinatorial regulatory role in the fetal DP phenotype. Further investigation into these regulators is warranted to determine if these proteins and/or associated pathways plays a role in the maintenance or modulation of DP cells to induce hair regeneration.
Project description:RNA-Seq of human fetal and adult scalp hair follicle dermal papilla (DP), dermal sheath cup (DSC), and interfollicular dermal (IFD) cells
Project description:Here we have developed a novel FACS strategy to prospectively isolate hair follicle dermal stem cells, dermal sheath and dermal papilla cells from adult skin initiating synchronous hair follicle regeneration and identified Hic1 as a marker of hfDSCs and Rspondins as stimulators of hfDSCs and epithelial cells, and subsequently hair follicle regeneration
Project description:Tissue homeostasis requires the balance of growth by cell production and regression through cellular loss. In the hair cycle during follicle regression, the niche traverses the skin through an unknown mechanism to reach the stem cells and prime regeneration. Here, by cell specific ablation and intravital imaging in live mice, we identify the follicle-lining dermal sheath as the key driver of tissue regression and niche relocation via smooth muscle contractile machinery that generates centripetal constriction force. We reveal the calcium/calmodulin/myosin light chain kinase pathway as the mechanism of sheath contraction that when blocked inhibits follicle contraction and impedes regression and niche relocation. Thus, our study identifies the dermal sheath as a smooth muscle that drives regression for reuniting niche and stem cells to regenerate tissue structure during homeostasis.
Project description:Single-cell proteomics data of dermal sheath cells (DSCs) during wound healing, generated using SCoPE2-MS, highlighting dynamic protein expression and functional changes across different healing stages.
Project description:Progenitor cell death and dermal papilla relocation during the regression phase of the hair growth cycle are essential for stem cell activation and follicle regeneration. This drastic follicle remodeling is coordinated by dermal sheath (DS) smooth muscle contraction, but how DS-generated forces are regulated is unknown. Here, we identify endothelin signaling - a potent vasoconstriction-regulating pathway - as the key activating mechanism of DS contraction. Pharmacological blocking or genetic ablation of both endothelin receptors, ETA and ETB, impedes DS contraction and halts follicle regression. Progenitors at the epithelial strand bottleneck are the main source of endothelin ligand ET-1, which is required for follicle regression. ET signaling in DS cells and downstream contraction is dynamically regulated by cytoplasmic Ca2+ levels via cell membrane and sarcoplasmic reticulum calcium channels. Together, these findings illuminate an epithelial-mesenchymal-interaction paradigm in which progenitors - before undergoing programmed cell death - control the contraction of the surrounding sheath smooth muscle to orchestrate homeostatic tissue regression and follicle reorganization.