Cutaneous homeostasis: a balancing cross-talk between epidermal stem cell pool and regulatory pathways

The skin is a sophisticated organ that has evolved several defense mechanisms, including physical, chemical, and microbiological barriers. Different stem cells (SCs) maintain the homeostasis of the epidermis’s various compartments to balance the states of activity, dormancy, and lineage commitment. Homeostasis describes the continuous renewal of the epidermis, which contains nails, sweat glands, and the pilosebaceous unit, which is composed of follicle and shaft of hair, arrector pili muscle, and sebaceous gland. There are many SCs in the skin and its parts, which suggests that the skin can heal and grow back quickly after a wound. The presence of a broad range of SCs in the skin and its appendages suggests that the skin has an exceptional capacity for regeneration and wound healing. SCs in the epithelial tissues endorse keratinocytes through regular differentiation. The molecular signals, including Wnt and bone morphogenetic protein (BMP) signaling, stimulate the hair follicle (HF) SCs by regulating the epithelial–mesenchymal interplay that underlies epithelial homeostasis. SCs and their pathways regulate skin development and homeostasis. To aid wound healing, Wnt can activate the synthesis of microtubule-binding proteins that keep microtubules at the point of the wounds active. In various body tissues, including the skin, the BMP family secretes signaling molecules from the transforming growth factor-β family that control cell division, proliferation, and apoptosis. Sonic hedgehog is the primary signaling system involved in cell proliferation and epithelial–mesenchymal interaction required for the development of follicle. Through qualitative and quantitative transcriptional regulation of various interfollicular epidermis and HFs, the Notch signaling pathway significantly contributes to regulating and maintaining skin homeostasis and developing the epithelial barrier. SC therapy has many applications, including dermal wound healing, hair growth, and in antiaging process. Recently, there has been progress in the field of human SCs across many fields of biology and medicine.