Hair follicle stem cells (HFSCs) reside in the bulge region of the outer root sheath of the hair follicle. They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity. The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions, wound repair and skin regeneration. The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways, such as lymphoid enhancer factor/T-cell factor, Wnt/β-catenin, transforming growth factor-β/bone morphogenetic protein, Notch and Hedgehog. The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied, but many mechanisms are still unclear. This article reviews the regulation of hair follicles, HFSCs and related signaling pathways, with the aims of summarizing previous research results, revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.

Cellular differentiation, the fundamental hallmark of cells, plays a critical role in homeostasis. And stem cells not only regulate the process where embryonic stem cells develop into a complete organism, but also replace ageing or damaged cells by proliferation, differentiation and migration. In characterizing distinct subpopulations of skin epithelial cells, stem cells show large heterogeneity and plasticity for homeostasis, wound healing and tumorigenesis. Epithelial stem cells and committed progenitors replenish each other or by themselves owing to the remarkable plasticity and heterogeneity of epidermal cells under certain circumstance. The development of new assay methods, including single-cell RNA sequence, lineage tracing assay, intravital microscopy systems and photon-ablation assay, highlight the plasticity of epidermal stem cells in response to injure and tumorigenesis. However, the critical mechanisms and key factors that regulate cellular plasticity still need for further exploration. In this review, we discuss the recent insights about the heterogeneity and plasticity of epithelial stem cells in homeostasis, wound healing and skin tumorigenesis. Understanding how stem cells collaborate together to repair injury and initiate tumor will offer new solutions for relevant diseases. Graphical Schematic abstract of cellular heterogeneity and plasticity of skin epithelial cells in wound healing and tumorigenesis

Wound healing is a complex biological process involving multiple cell types with their critical functions. The diabetic wounds show delayed wound healing, while the anagen wounds display accelerated wound closure. However, the mechanisms underlying the effect of cellular heterogeneity on wound healing are still unclear. CD34+ cells exhibit high heterogeneity in wound skins and improve wound healing. Herein, we investigated the phenotypic and functional heterogeneity of CD34+ cells in normal, anagen, and diabetic wounds. We obtained CD34 lineage tracing mice, constructed distinct wound models, collected CD34+ cells from wound edges, and performed single-cell RNA sequencing. We identified 10 cell clusters and 6 cell types of CD34+ cells, including endothelial cells, fibroblasts, keratinocytes, neutrophils, macrophages, and T cells. 5 subclusters were defined as fibroblasts. The CD34+ fibroblasts C2 highly expressed papillary fibroblastic markers took up the largest proportion in anagen wounds and were associated with inflammation and extracellular matrix. Increased CD34+ endothelial cells, fibroblasts C4, and neutrophils as well as decreased fibroblasts C1 were discovered in diabetic wounds. We also filtered out differentially expressed genes (DEGs) of each cell cluster in anagen wounds and diabetic wounds. Functional enrichment analysis was performed on these DEGs to figure out the enriched pathways and items for each cell cluster. Pseudotime analysis of CD34+ fibroblasts was next carried out indicating fibroblast C4 mainly with low differentiation. Our results have important implications for understanding CD34+ cell type-specific roles in anagen and diabetic wounds, provide the possible mechanisms of wound healing from a new perspective, and uncover potential therapeutic approaches to treating wounds. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Pyroptosis is an inflammatory form of programmed cell death closely related to tumor formation and development. However, the functional role and significance of pyroptosis in HCC remain unclear. Methods RNA-sequencing and clinical data for HCC patients were obtained from TCGA and GEO databases. We first explored the 49 pyroptosis-related genes (PRGs) expression patterns in HCC. The univariate Cox regression analysis and consensus clustering by PRGs were then performed to divide TCGA-HCC patients into two subtypes, C1 and C2. Based on prognostic PRGs, the LASSO Cox regression method was employed to construct a prognostic model. The predictive value was evaluated by generated nomogram and decision curve analysis (DCA). GSEA and immune infiltration analysis evaluated immune status. Additionally, regulating networks of prognostic PRGs were predicted with Networkanalyst online tools. Finally, the expression of the prognostic genes was validated by qRT-PCR. Results HCC patients in subtype C2 exhibited a larger proportion of grade III-IV, higher immune scores, more genetic mutations, and increased expression of immune factors. A prognostic model was developed based on four prognostic PRGs and classified HCC patients into high- and low-risk groups. Patients in the low-risk group showed better prognostic survival. The risk score of this model was an independent prognostic factor and had a good predictive ability. Besides, immune status showed a difference between the two risk groups. We drew the regulating networks between the mRNA of 4 prognostic PRGs and TFs, miRNAs, or chemicals. The qRT-PCR results demonstrated PRGs highly expressed in paracancerous tissues and lowly expressed in carcinoma. Conclusions The prognostic model based on four PRGs has significant implications for prognosis assessment and provides a new idea for HCC treatment.