Deciphering the molecular mechanisms of stem cell dynamics in hair follicle regeneration

Abstract

Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The crucial function of hair follicle stem cells is to maintain these hair growth cycles. Another vital aspect is the activity of melanocyte stem cells, which differentiate into melanin-producing melanocytes, contributing to skin and hair pigmentation. Sebaceous gland stem cells also have a pivotal role in maintaining the skin barrier by regenerating mature sebocytes. These stem cells are maintained in a specialized microenvironment or niche and are regulated by internal and external signals, determining their dynamic behaviors in homeostasis and hair follicle regeneration. The activity of these stem cells is tightly controlled by various factors secreted by the niche components around the hair follicles, as well as immune-mediated damage signals, aging, metabolic status, and stress. In this study, we review these diverse stem cell regulatory and related molecular mechanisms of hair regeneration and disease conditions. Molecular insights would provide new perspectives on the disease mechanisms as well as hair and skin disorder treatment.

Immune niches for hair follicle development and homeostasis

“…Another important feature of the hair follicle is immune privilege ( Paus et al, 2003 ; Bertolini et al, 2020 ; Lee and Choi, 2024 ). The immune privilege is a set of mechanisms that prevent or suppress active cytotoxic attacks from immune cells to prevent potential damage of organs by inflammatory processes.…”

Hair follicle stem cells promote epidermal regeneration under expanded condition

“…Recently, a study showed that when a superficial wound was created in mice, the HF cells in the newly formed epidermis were gradually replaced by keratinocytes derived from the epidermis ( Ji et al, 2021 ). It is indicated that HFSCs in the bulge region predominantly react to epidermal wounds by generating short-lived “transient amplifying” cells, which play a part in the recovery of acute wounds ( Lee and Choi, 2024 ). Langton et al reported that when a wound was created in the tail of mutant mice lacking all HF development, the cutaneous wounds healed with a delay re-epithelialization ( Langton et al, 2008 ).…”

“…Hence, the importance of epidermal stem cells lies in their ability to repair skin defects, restore skin integrity, enhance tensile strength, and improve barrier function ( Singer et al, 1999 ). During wound healing and skin regeneration, epidermal stem cells acquire the ability to repair adjacent compartments, and these compartments can be refilled with each other ( Sada et al, 2016 ; Hirsch et al, 2017 ; Lee and Choi, 2024 ). Observed that mechanical stretching and epidermal stem cells are closely correlated and regulated by EZH2 ( Wang et al, 2021 ; Wang et al, 2021 ).…”

The Potential Reversible Transition between Stem Cells and Transient-Amplifying Cells: The Limbal Epithelial Stem Cell Perspective

“…The mesenchymal components of the HF, i.e., the dermal sheath, also contain SCs called dermal sheath mesenchymal stem cells or HF dermal stem cells that are capable of self-renewal and regeneration of the dermal sheath compartment after catagen [116]. The HF-associated sebaceous glands also contain Lrig1+ SCs and SCD1+ proliferative progenitor cells that differentiate into sebocytes [117]. The markers of different SCs within the HF components include CD200 (human), CD34, K19, Sox9, Lgr5, Hopx, Nfatc, Tcf, Lhx2 and Gli1 for the bulge SCs; Lgr6, Lrig1 and MTS24 for the isthmus SCs; Blimp1 for the sebaceous gland and Sca1 for the infundibulum [118].…”