At least six protein subtypes of p63 exist, and these are divided into two groups based on transcription activation (TA): TA subtype (TA-p63α, TA-p63β, and TA-p63γ) and N-TA subtype (ΔN-p63α, ΔN-p63β, and ΔN-p63γ) . affect stem cell mainte-nance and behaviour. In the therapy of chronic wounds, they can be administrated either topically or using different matrix like hydrogels, scaffolds, dermal substitutes and extracellular matrix (ECM) derivatives. Epidermal stem cells are responsible for maintaining skin homeostasis. Although EpiSCs have the self-renewal and multilineage differentiation potentials, more efforts should still be made regarding the effective separation of EpiSCs. Studies have demonstrated [16–18] that the decrease in β1 integrin expression stimulates hair follicle stem cells to leave the stem cell pool and migrate upward into differentiated cells [19, 20]. Increasing evidence shows that miRNAs are stably present in body fluids, including saliva, urine, breast milk, and blood, and are involved in the circulation of exosomes . -, Korbling M., Estrov Z. We treated mouse ESCs isolated from skin tissues with curcumin, and then assessed the proliferation ability of cells induced by epidermal growth factor using cell counting kit‐8 assay. USA.gov. Integrin comprises one α subunit and one β subunit; different α and β subunits form a variety of different integrins. One has the characteristics of stem cells themselves, and the other one differentiates into transient amplifying cells (TACs). As the biggest organ in the body, skin tissues represent a larger reservoir for adult stem cells. 2. This study aimed to elucidate the regulatory mechanism by which hypoxia acts on EpSCs. Induction of basal cell carcinoma 2 P311 Accelerates Skin Wound Reepithelialization by Promoting Epidermal Stem Cell Migration Through RhoA and Rac1 Activation Wound Healing from Dermal Grafts Containing CD34+ Cells Is Comparable to Wound Healing with Split-Thickness Skin Micrografts Plastic and Reconstructive Surgery, Vol. Hildebrand et al. However, it has been proved that skin stem cells (predominantly epidermal stem cells (EpiSCs) and hair follicle stem cells) distributed in the basal layer of the epidermis and the hair follicle bulge are important sources of cells for regeneration, metabolism, and wound repair of skin. 1. Stem cells had a therapeutic effect on wound healing; however, the mechanism of action of EpiSCs on wound healing is poorly understood . Local stem cells can also be transformed into keratinocytes, sebaceous gland, and other skin-associated tissues. TINCR regulates epidermal differentiation by binding to Staufen 1 to form a complex that increases the stability of mRNAs promoting differentiation (e.g., KRT80, MAF, and MAFB) . The continuous activation of the Notch signaling pathway can upregulate the transcription of the HES1 gene, thereby inhibiting the transcription of the target gene . We aimed to explore the effect of curcumin on epidermal stem cells (ESCs) in regulating wound healing and the underlying molecular mechanism. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. The authors declare that they have no conflict of interest. . This study aimed to elucidate the regulatory mechanism by which hypoxia acts on EpSCs. Multi-potent mesenchymal stem cells (MSCs) give rise to many tissue lineages and have been implicated in wound healing making them a potential candidate for cell-based bioengineered products for in … The development of new wound therapies, such as bioengineered skin equivalents, is an ongoing process. Dr. Beri will also touch on the latest applications of epidermal stem cells in skin grafting. The success of laboratory applications shows the application prospects of EpiSCs in various clinical scenarios. Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. -, Qi S. H., Liu P., Xie J. L., et al. A quick procedure using non-cultured autologous epidermal cells for wound healing was also reported [5, 109]. Epidermal wound healing refers to the repair of the epidermis in response to wounding. However, the expression of miR-203 was upregulated in chronic wounds [96, 97]. Recent studies have reported a regulatory effect of lncRNA on the functions of keratinocytes and epidermal cells in the skin . relevant investigations also demonstrated that Scs exert e Long non‑coding RNA HOTAIR promotes burn Julin et al. Related reports have suggested that, in animal models, the transplantation of EpiSCs can treat LSCD with a cure rate of 80% . For example, miR-200 (a, b, and c), miR-141, miR-429, miR-19b, and miR-20 are expressed in the whole layer of epidermal tissue, while the expression of the miR-199 family can only be detected in hair follicles [90, 91]. ... Esmaeilzade B, Nobakht M, Joghataei MT, et al. Nature Communications , February 2017 … Many markers are now used to identify EpiSCs, but no markers have been found that can separate EpiSCs at the single-cell level. Wnt signaling protein is a secreted glycoprotein that plays an important role in maintaining metabolic homeostasis . HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling. During this period, related proteins, RNA, and genomic DNA are needed to synergistically regulate the gene expression. Recent studies have found many similarities between the cornea and cutaneous epithelial tissues, including typical stratified epithelial morphology and expression of p63. The normal human skin has a variety of stem cells with multilineage differentiation potentials. GDF-5, also known as BMP-14, is a member of the BMP family and can be used as a self-renewal supporter. -. For deep wounds, scar hyperplasia inevitably occurs after healing due to the loss of most of the skin stem cells . The specific knockout of ANCR gradually results in an increase in the expression of transcription factors that promote differentiation, such as Grainyhead-like 3 (GRHL3), zinc finger protein 750 (ZNF750), positive regulatory domain 1 (PRDM1), and Kruppel-like factor 4 (KLF4), thus leading to the premature differentiation of the epidermis [115, 116]. Thus, hair follicle and its connective tissue sheath are attractive targets for the development of regenerative therapies due to its accessibility and richness of stem cells. 2020, Article ID 9148310, 11 pages, 2020. https://doi.org/10.1155/2020/9148310, 1Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China, 2Department of Medical Cosmetology, Jiangxi Maternal and Child Health Hospital, Nanchang 330006, China, 3Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 512100, China. HHS 3. This indicates that the outcome of wound healing is not only related to the number of skin stem cells but also their differentiation behaviors. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. The EMBO Journal. A. Epidermal stem cells arise from the hair follicle after wounding. CD34+ stem cells, Diabetic foot ulcers, Angiogenesis. The binding of the Wnt protein to the transmembrane receptor blocks GSK-3β-mediated phosphorylation of β-catenin, resulting in the accumulation of β-catenin in the cytoplasm. Nucleoprotein p63 is a homologous gene transcription factor of p53, and its structure and function are similar to those of p53. Morphologically, EpiSCs have the characteristics of undifferentiated cells: relatively small cell volume, large nucleus with less cytoplasm, high nuclear to cytoplasmic fluorescence ratio, low intracellular RNA content, fewer and immature organelles, and relatively stable position in tissue structure . | At present, tissue-engineered EpiSCs have been used as a potential treatment, but their long-term efficacy and related clinical trials still need further investigation. doi: 10.1093/emboj/20.6.1215. Sign up here as a reviewer to help fast-track new submissions. 2018 Nov 1;6(11):2859-2870. doi: 10.1039/c8bm00934a. We are committed to sharing findings related to COVID-19 as quickly as possible. We conclude that follicular cells can undergo reprogramming to become long-term repopu- lating epidermal progenitors following wounding.— Levy, V., Lindon, C., Zheng, Y., Harfe, B. D., Morgan, B. Epidermolysis bullosa (EB) is a serious skin disease caused by mutations of genes involved in the regulation of the adhesion of basal epithelial cells to the basal layer. There are 4 phases of wound healing, and there are factors that can impact the rate at which […] As the largest org an and first ba rrier in the bod y, the skin. Skin wound healing is a highly organized and coordinated series of processes that results in the restoration of tissue integrity and functions. Nestin expression in hair follicle sheath progenitor cells. For example, skin epithelial appendages contribute epidermal cells for wound healing. We first isolated … As early as in 1992, the researchers attempted to transplant cultured keratinocytes and melanocytes to treat stable vitiligo . Vinaik R, Jeschke MG. Burn-derived Mesenchymal Stem Cells in Wound Healing. The different degrees of differentiation of epidermal cells can be used to express different characteristics of keratin, which can be used for identifying EpiSCs, TACs, and TDCs . A. G. L. van Buggenum, and K. W. Mulder, “BLNCR is a long non-coding RNA adjacent to integrin beta-1 that is rapidly lost during epidermal progenitor cell differentiation,”, W. Chen, W. W. Zhang, C. Shi, X. Lian, S. Yi, and T. Yang, “Enrichment of epidermal stem cells of rats by Vario magnetic activated cell sorting system,”, C. Won, Y. M. Jeong, S. Kang et al., “Hair-growth-promoting effect of conditioned medium of high integrin, E. Metral, N. Bechetoille, F. Demarne, W. Rachidi, and O. Damour, “, K. Lorenz, T. Rupf, J. Salvetter, and A. Bader, “Enrichment of human, H. Tani, R. J. Morris, and P. Kaur, “Enrichment for murine keratinocyte stem cells based on cell surface phenotype,”, D.-S. Kim, H. J. Cho, H. R. Choi, S. B. Kwon, and K. C. Park, “Isolation of human epidermal stem cells by adherence and the reconstruction of skin equivalents,”, X. Zhou, G. Li, D. Wang, X. In addition, it is also involved in the cell-to-cell adhesion . Moreover, α6briCD71dim cells have also been found in human skin. The sources of EpiSCs may be as follows: (1) storage in the basal layer with rich blood supply in the epidermis; (2) stem cells in the hair follicles, which are the warehouse of EpiSCs; (3) reverse production from differentiated cells; (4) regeneration of mesenchymal cells into EpiSCs; (5) induced differentiation of embryonic stem cells; and (6) migration of hematopoietic stem cells or other tissue stem cells to the skin tissue with the blood circulation under the stimulation of certain factors, which transversally differentiate into EpiSCs due to the plasticity of stem cells. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. The findings indicated that differentially expressed lncRNAs were involved in the regulation of epidermal cell proliferation and differentiation by regulating related transcription factors or increasing the stability of related mRNAs. MSCs show the ability to differentiate into different cells of the epidermis. Ease of availability, isolation and in vitro expansion make MSCs the best candidates for wound‐healing therapies in comparison with other stem cells including embryonic stem cells (ESCs). Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications. They are small cell populations with a high nuclear to cytoplasmic ratio and still have the ability to produce a large number of cell populations after 10 days of in vitro culture. However, a role for Rac1 in the maintenance of epidermal stem cells seems clear (20, 33, 35), and reduced wound healing in the Rac1-deficient epidermis may result, in part, from loss of a stem cell compartment that is required for rapid epidermal expansion . In addition, many studies have detected the differential expression of lncRNAs between early-passage and late-passage dermal papilla, with the latter losing the ability to induce hair growth in the body. The microenvironment of stem cells, also known as “stem cell niches,” plays a key role in regulating the migration, proliferation, and differentiation of stem cells, and this effect is achieved by a network system of multiple intertwined signaling pathways . While cell lineages of the bulge (brown), infundibulum (orange), and interfollicular epidermis (white) enter more as a cohesive cell population (solid arrows), sebaceous duct cells (blue) migrate to the wound site suprabasally as individual cells (dashed arrow) (1). Epidermal Stem Cells in Skin Wound Healing Yuanyuan Li,* Jamie Zhang, Jiping Yue, Xuewen Gou, and Xiaoyang Wu* Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois. As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. The superﬁcial layer of the epidermis, the stra- At present, great progress has been made in the study of epidermal stem cells at the cellular and molecular levels. doi: 10.1016/j.burns.2007.04.003. During tissue injury, WNT ligands are highly expressed during the early phases of wound healing and promote migration of epithelial cells. Stem cell transplantation is reported to promote skin healing, endothelial cell transformation, and vascular formation. FASEB J. Gene Therapy Approaches in Wound Healing. Lyle et al. Currently, clinical studies on the application of EpiSCs are available on the official website of the clinical trial (http://clinicaltrials/gov/). In contrast, the high expression of α6-integrin and low expression of transferrin receptor (α6-bright/CD71-dim) are widely recognized means for identifying EpiSCs to date [25, 26]. miRNAs transmit information through exosomes, which is considered to be the third pathway for intercellular signaling, as important as the other two pathways: cellular contact-dependent signal transduction and soluble molecular-mediated conduction [100–102]. doi: 10.1126/science.1092436. NIH However, the mechanism of action of epidermal stem cells on wound healing and regeneration is not completely clear. of stem cells . Ronghua Yang and Jingru Wang contributed equally to this work. In this paper, we review the characteristics of EPSCs and the mechanisms underlying their functions during wound healing. Clipboard, Search History, and several other advanced features are temporarily unavailable. Expression of Lgr5 marks stem cells located in the HF bulge and hair germ. During the repair of skin wounds, the Wnt/β-catenin signaling pathway is activated, and the wound surface is covered by the stratified epithelium. Sun, and X. Li, “Cytokeratin expression in epidermal stem cells in skin adnexal tumors,”, M. Michel, N. Torok, M. J. Godbout et al., “Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage,”, M. Michel, N. L'Heureux, F. A. Auger, and L. Germain, “From newborn to adult: phenotypic and functional properties of skin equivalent and human skin as a function of donor age,”, M. R. El-Hadidy, A. R. El-Hadidy, A. Bhaa, S. A. Asker, and S. A. Mazroa, “Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO, D. Chen, Y. Qu, X. Hua et al., “A hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo expansion of human corneal epithelial stem cells,”, S. Lyle, D. E. Elder, M. Christofidou-Solomidou, Y. Liu, S. Albelda, and G. Cotsarelis, “Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype,”, M. T. Cerqueira, A. M. Frias, R. L. Reis, and A. P. Marques, “Interfollicular epidermal stem cells: boosting and rescuing from adult skin,” in, R. L. Zhang, J. X. Meng, C. X. Liu et al., “Genome-wide screen of promoter methylation analysis of ES cells and ES derived epidermal-like cells,”, S. Nagosa, F. Leesch, D. Putin et al., “microRNA-184 induces a commitment switch to epidermal differentiation,”, J. L. Xie, T. Z. Li, S. H. Qi et al., “Study of the localization of epithelial stem cells in normal skin on the wound healing,”, L. Rinaldi, D. Datta, J. Serrat et al., “Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis,”, N. Ojeh, B. Akgul, M. Tomic-Canic, M. Philpott, and H. Navsaria, “In vitro skin models to study epithelial regeneration from the hair follicle,”, J. M. Pattison, S. P. Melo, S. N. Piekos et al., “Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment,”, Z. F. Song, D. Liu, Y. Peng et al., “Expression of microRNA-203 and P63 in human epidermal stem cells and keratinocytes,”, G. Pellegrini, E. Dellambra, O. Golisano et al., “p63 identifies keratinocyte stem cells,”, J. W. Shin, H. R. Choi, K. M. Nam et al., “The co-expression pattern of p63 and HDAC1: a potential way to disclose stem cells in interfollicular epidermis,”, A. Spradling, D. Drummond-Barbosa, and T. Kai, “Stem cells find their niche,”, S. Fre, M. Huyghe, P. Mourikis, S. Robine, D. Louvard, and S. Artavanis-Tsakonas, “Notch signals control the fate of immature progenitor cells in the intestine,”, H. Zhang, X. Nie, X. Shi et al., “Regulatory mechanisms of the Wnt/, T. Jin, “Current understanding on Role of the Wnt signaling pathway effector TCF7L2 in glucose homeostasis,”, G. Xu, R. Emmons, D. Hernández-Saavedra, A. Kriska, Y. X. Pan, and H. Chen, “Regulation of gene expression of wnt signaling pathway by dietary high fat and effects on colon epithelia of male mice,”, P. Huang, R. Yan, X. Zhang, L. Wang, X. Ke, and Y. Qu, “Activating Wnt/, J. Among other Regenerative Medicine basics, she discusses properties of epidermal stem cells, the physiology of wounds and the role of epidermal stem cells in wound healing. Epidermal only wounds are typically less severe than those affecting the dermis and so stages of the wound healing response may be missed. miR-203 plays a role in maintaining the morphology of skin tissues and differentiation of keratinocytes through inhibiting the expression of p63 and leading to the loss of characteristics of EpiSCs and premature differentiation [93–95]. However, if the laser confocal microscope is used to observe at the level of monolayer cells, or flow cytometry and fluorescence-activated cell separation are used in combination, the difference in the positive expression intensity of β1 integrin between the two cells can be identified, thus achieving the identification of EpiSCs and TACs [22, 23]. Hence, they have important clinical values in the regeneration treatment of other epithelial tissues. NLM FASEB J. 2015 Oct 23;16(10):25476-501. doi: 10.3390/ijms161025476. 35. The latest findings indicate the huge therapeutic potential of stem cells in regenerative medicine, including the healing of chronic wounds. Mice lacking the VDR when placed on a low calcium diet have delayed wound healing. Main stem cell types involved in wound healing process are: epidermal and dermal stem cells, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and hematopoietic stem cells (HSCs). Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors. Ghazizadeh S., Taichman L. B. Local stem cells can also be transformed into keratinocytes, sebaceous gland, and other skin-associated tissues. When the extracellular domain of Notch binds to the ligand, the Notch receptor protein undergoes three steps of cleavage after an enzymolysis process involving the γ-secretase, releases the activated form of the Notch intracellular domain (NICD), and then enters the nucleus to bind to the CSL (CBF1, Suppressor of Hairless, Lag-1), a DNA-binding protein, to activate the expression of the target genes . 4,6-diamidino-2-phenylindoleindole (DAPT), as a blocker of the Notch signaling pathway, can specifically block the action of γ-secretase, thereby preventing the activation of Notch . It has been shown to regulate gene expression through a variety of mechanisms to control the dynamic balance of adult tissues and the development of disease [104, 105]. Skin stem cells distributed in the basal layer of the epidermis and hair follicles are important cell sources for skin development, metabolism, and injury repair. 103 It further discussed the mechanism of action and the development direction in the future. Currently, a consensus has been reached worldwide that transplanting CES into patients with extensive burns can increase their survival rate  because CES is rich in EpiSCs, which can undergo proliferation and differentiation after transplanting into wounds, thus achieving epidermal tissue regeneration . J Dermatol & Skin Sci. The immortalized human bulge stem cell line Tel-E6E7  was kindly provided by Dr. Lyle (University of Massachusetts Medical School) and cultured in the same conditions. Ronghua Yang, Jingru Wang, Xiaodong Chen, Yan Shi, Julin Xie, "Epidermal Stem Cells in Wound Healing and Regeneration", Stem Cells International, vol. Ronghua Yang, 1. 101 WNT signaling is also necessary for formation of new hair follicles during cutaneous wound healing by driving self-renewal of interfollicular epidermal stem cells 102 and initiating de-differentiation of epidermal cells to follicular progenitor cells. In the recent two decades, related studies have revealed important regulatory roles of many noncoding RNAs (ncRNAs) in cell physiology and pathology . Due to high cost of single-cell RNA-seq experiments and the low efficiency of wound cell identification using this approach (more than 1000 cells needed to be sequenced to identify around 100 wound cells for each background), we performed for most wound healing time points one biological experiment in both Lgr5 and Lgr6 mice (only exception Lgr5 1 day PWI: two mice). Instant cell adaptations of Lgr5 cells within their original niche permit interactions with the wound environment, an ability Lgr6 cells already possess before wounding. The New England Journal of Medicine. As the contributions of EPSCs in wound healing and tissue regeneration have been increasingly attracting the attention of researchers, a rising number of therapies based on EPSCs are currently under development. Epidermal growth factor promotes mesenchymal stem cell-mediated wound healing and hair follicle regeneration. Xiaodong Chen, 1. Li L, Mignone J, Yang M, et al. A preliminary study on the identification and distribution of epidermal stem cells in different degrees of burn wounds in scalded rats. Cédric Blanpain et al. lncRNA is an ncRNA with more than 200 nucleotides that contains numerous and diverse ncRNA molecules . Defining stem cell dynamics and migration during wound healing in mouse skin epidermis. Epidermal stem cells (EPSCs) are a multipotent cell type and are committed to the formation and differentiation of the functional epidermis. Qi C, Xu L, Deng Y, Wang G, Wang Z, Wang L. Biomater Sci. It plays an important role in regulating the differentiation of EpiSCs [82, 83]. Epidermal stem cells are relatively quiescent and undifferentiated with a capacity to maintain homeostasis, self-renew tissue, and contribute to wound repair. The Notch receptor must be hydrolyzed and cleaved by the protease γ-secretase to release the intracellular domain, thereby activating the signaling pathway. Zhonghua Shao Shang Za Zhi. Chen, and S. C. G. Tseng, “Mesenchymal stem cells derived from human limbal niche cells,”, I. L. Weissman, D. J. Anderson, and F. Gage, “Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations,”, J. R. Bickenbach, “Identification and behavior of label-retaining cells in oral mucosa and skin,”, K. Rzepka, G. Schaarschmidt, M. Nagler, and J. Wohlrab, “Epidermal stem cells,”, J. L. Sherley, “Asymmetric cell kinetics genes: the key to expansion of adult stem cells in culture,”, T. Shibuya, M. Honma, M. Fujii, S. Iinuma, and A. Ishida-Yamamoto, “Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of, F. M. Watt, “Stem cell fate and patterning in mammalian epidermis,”, X. D. Chen, L. I. Tian-Zeng, and Q. I. Shao-Hai, “p63 and, P. H. Jones and F. M. Watt, “Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression,”, J. Zhu, P. Wang, Z. Yu et al., “Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells,”, W. F. Bai, W. C. Xu, H. X. Zhu, H. Huang, B. Wu, and M. S. Zhang, “Efficacy of 50 Hz electromagnetic fields on human epidermal stem cell transplantation seeded in collagen sponge scaffolds for wound healing in a murine model,”, R. Zhan, F. Wang, Y. Wu et al., “Nitric oxide induces epidermal stem cell de-adhesion by targeting integrin, P. Kaur and A. Li, “Adhesive properties of human basal epidermal cells: an analysis of keratinocyte stem cells, transit amplifying cells, and postmitotic differentiating cells,”, A. Li, P. J. Simmons, and P. Kaur, “Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype,”, S. E. J. Tanis, E. S. Köksal, J. We discuss in this chapter the recent progress that has been made in the identification of SC from the skin epidermis, the role played by epidermal SC during homeostasis and wound healing, the therapeutic use of skin stem cells to treat patients suffering from extensive burns or hereditary skin diseases. [Biology of epidermal stem cells: impact on medicine]. However, the mechanism of action of epidermal stem cells on wound healing and regeneration is not completely clear. EpiSCs express mainly keratin 15 and 19 (CK15 and CK19); TACs express keratin 5 and 14 (CK5 and CK14); and TDCs express keratin 1 and 10 (CK1 and CK10). Skin stem cells distributed in the basal layer of the epidermis and hair follicles are important cell sources for skin development, metabolism, and injury repair. A high level of Wnt signaling can induce stem cells to develop into structures of hair and sebaceous gland, while blocking Wnt signaling leads to the differentiation of EpiSCs in the epidermis . Inflammatory reaction the stratified epithelium maintain homeostasis, self-renew tissue, abundant inflammatory cell,! Low specific expression of miR-203 was upregulated needed to synergistically regulate the of! Of Notch receptor in mammals, is the cytoplasmic protein β-catenin repair and scar formation remain unclear there thick... Notch1 is widely and selectively expressed in epidermal progenitor cells and their clinical applications years, the of. Provide satisfactory wound healing through differentiation and migration during wound healing shh is not limited to regenerating stratified.. 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