Nerve–stem cell crosstalk in skin regeneration and diseases

The peripheral nervous system tightly interacts with skin, forming a nerve-derived niche for regulating skin stem cells during development and regeneration. During skin morphogenesis, signals from epithelial tissues such as hair follicles coordinate with mesenchymal cues to facilitate the formation and maintenance of skin innervation. In adulthood, signals from cutaneous nerves influence the behaviors of skin stem cells, coupling regenerative activities in the skin with fluctuations from the body and the external world. Aberrant nerve–stem cell interactions are implicated in multiple skin diseases, including skin cancer and hair disorders, providing potential therapeutic targets for the development of novel treatment methods. Skin is the interface between the external environment and our body systems. It receives extensive innervation from the peripheral nervous system (PNS), which enables the skin to sense and respond to various stimuli such as touch and temperature. Recent studies have revealed unanticipated functions of cutaneous nerves in orchestrating stem cell behaviors and tissue regeneration. Diverse types of nerve fibers interact closely with different stem cell populations in the skin, specifying a nerve-derived niche for stem cell regulation. Here, we review recent discoveries on the nerve–stem cell crosstalk from tissue morphogenesis to regeneration and diseases, highlighting a key role of peripheral nerves in coupling stem cell activities with fluctuations from the inner body and the external world. Skin is the interface between the external environment and our body systems. It receives extensive innervation from the peripheral nervous system (PNS), which enables the skin to sense and respond to various stimuli such as touch and temperature. Recent studies have revealed unanticipated functions of cutaneous nerves in orchestrating stem cell behaviors and tissue regeneration. Diverse types of nerve fibers interact closely with different stem cell populations in the skin, specifying a nerve-derived niche for stem cell regulation. Here, we review recent discoveries on the nerve–stem cell crosstalk from tissue morphogenesis to regeneration and diseases, highlighting a key role of peripheral nerves in coupling stem cell activities with fluctuations from the inner body and the external world. a bundle of smooth muscle cells that attaches to hair follicles and produces goosebumps upon sympathetic impulse. the shorter hair types than the guard hair, constituting ~23% of trunk hair follicles. most common form of skin cancer that usually originates from uncontrolled growth of skin stem cells. highly aggressive skin cancers that derive from malignant transformation of cutaneous epithelial cells. layer beneath the epidermis, providing mechanical support and thermo insulation. clusters of sensory neuronal cell bodies that extend sensory nerves to innervate the body trunk. basal cells at the innermost layer of skin epidermis, driving the self-renewal and regeneration of the stratified epidermis. outermost layer of the skin, which primarily consists of layers of epithelial cells and provides barrier functions against environmental insults. longest hair type that constitutes ~1% of hairs on the skin of the trunk and proximal limbs in most mammals, also referred as primary or tylotrich hairs. a protruded structure in a hair follicle that hosts HFSCs and McSCs. somatic stem cells that regenerate hair follicle and produce hair shaft. stratified epidermis between hair follicles. structure that wraps around the isthmus region of the hair follicle, constituted of lanceolate sensory nerve endings. stem cells that differentiate into pigment-producing melanocytes to color the hair and skin. a malignant skin cancer that originates from the melanocyte lineage. specialized keratinocytes in touch domes that are innervated by specific sensory nerve fibers to transmit the sense of indentation. small peptides synthesized and released by neurons to act as signaling molecules to surrounding cells. cohorts of secretory factors that promote the survival, maturation, and maintenance of nerve fibers. cohorts of cell types and secreted signals that surround, regulate, and control stem cells. bag-like structure below the bulge in the telogen hair follicle, hosting a group of HFSCs that are primed for activation. clusters of sympathetic neuronal cell bodies that extend sympathetic nerves to innervate target organs. specialized docking sites for sensory afferents that form in association with guard hairs. highly proliferative stem cell progenies that are responsible for tissue production as well as stem cell and niche regulation. clusters of sensory neuronal cell bodies that extend sensory nerves to innervate head and face. finest and most abundant hair type that constitute ~76% of trunk hair follicles in mammals.