Stem and progenitor cells in sebaceous gland development, homeostasis and pathologies

Abstract

Sebaceous glands (SGs) are acinar holocrine-secreting appendages of the epidermis and localize to most areas of the body surface. 1 Generally, SGs constitute a crucial component of the pilosebaceous unit and are intimately associated with the junctional zone (JZ), an area of the upper and permanent part of the hair follicle (HF). While the outer layer of the SG contains proliferative cells, the inner compartment is composed of sebocytes, specialized keratinocytes, that produce a mixture of an oily and waxy material, called sebum. [1][2][3] Upon differentiation and maturation of sebocytes, the lipidcontaining sebum is released by holocrine secretion through a specialized secretory duct of the gland into the follicular canal to reach the surface of the skin. 4 This complex mixture of lipids contributes significantly to the barrier function of mammalian skin by reducing water loss from the surface of the skin and facilitates water repulsion and thermoregulation. 1,5 Although all the details of the physiological complexity of SGs are not completely understood, sebum has antimicrobial activity, contains antioxidants and protects against UVB-induced apoptosis. 1,4,[6][7][8] Distinct regions of the skin and surface epithelium generate SGs independently from HF structures, e.g.

Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

“…[ 84,85 ] The SG also requires continuous self‐renewal to replenish differentiated sebocytes lost during holocrine sebum production. [ 78 ]…”

“…[84,85] The SG also requires continuous self-renewal to replenish differentiated sebocytes lost during holocrine sebum production. [78] One of the first abnormalities observed in rc mice is their greasy, unkempt hair coat, [86] suggestive of SG dysfunction resulting in excessive sebum secretion. Subsequent analysis of both the rc mice and Mpzl3 GKO mice revealed SG hypertrophy and production of excessive lipids (Figure 4F,G), likely caused by sebocyte hyperproliferation [21,23] (Wikramanayake et al under review).…”

“…Another implication could be in the modulation of SG functions and sebum production. The proper functioning of SGs is indispensable for normal skin homeostasis and barrier function, [78,81] and SG abnormalities are associated with acne vulgaris, cicatricial alopecia, chemotherapy-induced alopecia, psoriasis, seborrheic dermatitis and multiple benign or malignant SG tumors. [80,[128][129][130][131][132] Moreover, SG hyperplasia and excessive sebum production, which are directly correlated with basal layer sebocyte proliferation, [84] leading to oily scalp or facial skin (seborrhea), are common dermatologic concerns that have given rise to a specialized consumer product market, [133] while SG atrophy and insufficient sebum production (sebostasis) contribute to the pathology of human skin aging [134] and can cause major skin irritation/dermatitis sicca.…”

Skin stem cells in health and in disease

“…Sebaceous glands are fueled by stem cells located around the junctional zone of the hair follicle. Geueke and Niemann 79 provide a comprehensive review in this issue that details the role stem and progenitor display in the development and maintenance of the sebaceous glands and in potential pathologies related to sebaceous gland malfunction. By contrast, sweat glands normally have a low turnover rate once developed.…”

The hair follicle‐psoriasis axis: Shared regulatory mechanisms and therapeutic targets

“…The hair follicle-psoriasis connection: Overlapping drug effects defect of excessive differentiation of epithelial HF stem cells in the bulge and their progeny and of sebocyte progenitor cells: instead of maintaining an equilibrium between sebaceous, hair follicle and epidermal differentiation, may be pushed into an epidermal differentiation fate. This could be studied by quantitative immunohistomorphometry analyses for relevant key markers such as keratin 15, keratin 19, CD34 and Lrig1[176][177][178] in the distal HF epithelium, comparing both lesional and non-lesional psoriatic with healthy skin biopsies.…”