Transcriptional and signalling regulation of skin epithelial stem cells in homeostasis, wounds and cancer

Abstract

As the largest organ of the human body, our skin serves as a physical barrier between the individual and the environment. The skin preserves body fluid, guards against irradiation and pathogens and conducts sensations. The epidermis is composed of several epithelial layers. The basal cells attach to the basement membrane above the dermis, joined by hemidesmosomes and adherens junctions, and are home to the epidermal stem cells (EpdSCs), which undergo long-term self-renewal and continuously fuel the upward flux of differentiating cells, forming the skin barrier. 1 EpdSC progenies transition through the multiple differentiated layers, starting with the suprabasal spinous layer, rich in desmosomes 2 ; then the granular layer, containing keratohyalin and lamellar granules; and finally the stratum corneum, composed of flattened denucleated corneocytes with heavily crosslinked keratin cables and a cornified envelope, eventually sloughed off the skin surface. 3 Connecting to the epidermis are many epidermal appendages, among which the most abundant are the sweat glands and the pilosebaceous units. Sweat glands are responsible for thermoregulation, 4,5 while the pilosebaceous unit is composed of

The METTL3-m6A Epitranscriptome: Dynamic Regulator of Epithelial Development, Differentiation, and Cancer

“…Epithelia are found lining internal and external surfaces, such as the lining of the intestinal track and the surface of the skin, and form the major barriers between the internal and external environments. The different types of epithelia are characterized as being stratified, transitional, or glandular, and depending on the region of the body, the cells can vary in shape and amount of stratification [ 47 ]. These tissues can be present in either dry or wet environments, such as the epidermis, and the oral cavity, respectively.…”

“…Any dysregulation of this highly coordinated differentiation process can lead to hyperplasia, abnormal differentiation, and diseases ranging from the neoplastic (squamous cell carcinoma) to the inflammatory (i.e., psoriasis). Indeed, while significant progress has been made in unraveling many of the pathways and players involved in driving these processes across epithelial tissues, such as WNT, Notch, Sonic Hedgehog (Shh), and BMP signaling [ 49 , 50 , 51 ], as well as the master epithelial transcription factor p63 [ 47 , 53 ], the role for epigenetic regulation, and particularly that of RNA epigenetics, is poorly understood.…”

Skin stem cells in health and in disease

“…When EpSCs divide to self‐renew and differentiate, stem cells stay at the most basal layer while differentiated progeny move upward 49,63 . Decades of studies have elucidated diverse molecular mechanisms regulating EpSC self‐renewal and differentiation, as detailed in a comprehensive review by Guan et al 64 in this special issue. EpSCs also represent one of the key cellular sources for skin cancers such as squamous cell carcinoma and basal cell carcinoma, 65‐67 both of which are among the most common types of cancer worldwide.…”

“…Huang et al 31 demonstrate the process by which hair follicles repair themselves after chemotherapy‐induced injury. The review by Guan et al 64 also outlines genes and pathways regulating stem cell behaviours in wound healing, as well as the flexible transcriptional and epigenetic states seen in skin stem cells after injury. For readers interested in learning more about wound healing processes, we refer them to a focus theme issue in Experimental Dermatology that has an excellent collection of research articles and reviews on this topic ( https://onlinelibrary.wiley.com/toc/16000625/2017/26/2).…”

Skin epigenetics

“…In addition to the their importance in explaining cell fate changes in skin development and disease, 3 epigenetic mechanisms are of interest because they may mediate environmental effects in skin diseases. Despite the importance of genetic predisposition, the contributions of non-genetic, environmental effects are clear in common skin diseases, including atopic dermatitis and psoriasis.…”