Expression of epidermal stem cell markers in skin and adnexal malignancies

Quist, Sven R; Eckardt, Maximilian; Kriesche, André; Gollnick, Harald

doi:10.1111/bjd.14494

Cited by 25 publications

(14 citation statements)

References 49 publications

(117 reference statements)

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“…In addition to hair‐loss disorders, the SHG and bulge are of particular clinical relevance because they may give rise to at least some basal cell carcinoma (BCC) in human skin, and dysregulated Wnt signalling has also been implicated in BCC pathobiology . Clinically, this renders a systematic examination of Wnt signalling in these key epithelial progenitor cell compartments of human HFs important also from an oncological perspective.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Hawkshaw

Hardman

Alam³

et al. 2019

Br J Dermatol

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Summary Background The signals that induce anagen (growth) in ‘quiescent’ human telogen hair follicles (HFs) are as yet unknown. Their identification promises better targeted therapeutic hair growth interventions. Objectives Recognizing the central role of Wnt signalling in hair biology, the aim was to delineate the differential expression of key agonists, antagonists and target genes of this pathway during the telogen‐to‐anagen transformation of human scalp HFs. Methods This differential expression was studied by in situ hybridization in human telogen and early‐anagen scalp HF sections. Results On anagen induction, gene expression of the Wnt ligands WNT3, WNT4 and WNT10B, the Wnt ligand secretion regulator WLS, and the Wnt target genes AXIN2 and LEF1, is significantly increased within the secondary hair germ and the dermal papilla. Conversely, expression of the secreted Wnt inhibitor SFRP1 (secreted frizzled‐related protein 1) is reduced. Human epithelial HF stem cells upregulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation. Conclusions We provide the first evidence that key changes in Wnt signalling that drive murine anagen induction also occur in human scalp HFs, yet with notable differences. This provides a rational basis for Wnt‐targeting therapeutic interventions to manipulate human hair growth disorders. What's already known about this topic? Upregulation of Wnt agonists and downregulation of Wnt antagonists in the secondary hair germ and/or dermal papilla drives hair growth (anagen) induction in mice. Autocrine Wnt signalling in murine epithelial hair follicle stem cells is required to maintain their stem cell function. Reduction of Wnt ligands or increased expression of Wnt antagonists induces dysregulation of the murine hair follicle cycle and causes alopecia. What does this study add? This study demonstrates for the first time that key Wnt pathway regulatory agonists, antagonists and target genes, are expressed in the human telogen‐to‐early‐anagen transformation. On human anagen induction the Wnt ligands WNT3, WNT4 and WNT10B are increased in the regenerating epithelium, whereas the Wnt antagonist, SFRP1 (secreted frizzled‐related protein 1), is reduced. Human anagen induction has fundamental differences in the expression of Wnt ligands compared with the murine system. What is the translational message? Regulation of these Wnt ligands permits targeted therapeutic interventions in human hair growth disorders and informs development of new drugs that promote or suppress anagen induction.

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Section: Discussionmentioning

confidence: 99%

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Hawkshaw

Hardman

Alam³

et al. 2019

Br J Dermatol

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“…Specifically, investigating the neuronal and neuroendocrine regulation of SGs promises to contribute further to fields of broad biological interest, such as maintenance of stem cell niches (Liao & Nguyen, ; Füllgrabe et al ., ; Kretzschmar et al ., ), tumour development and progression (Kyllo, Brady & Hurst, ; Quist et al ., ), lipid synthesis (Guy, Ridden & Kealey, ; Schneider & Paus, ; Jester, Potma & Brown, ), autophagy (Fischer et al ., ; Rossiter et al ., ), and interaction of the nervous system with cardinal signalling pathways in peripheral tissues, i.e. Hedgehog (Allen et al ., ; Brownell et al ., ), Wingless (Kretzschmar et al ., ; Lim et al ., ), and Hippo pathway signalling (Yosefzon et al ., ).…”

Section: Major Open Questions and Translational Relevance Of Neuro‐rementioning

confidence: 99%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

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“…28 A study by Quist et al showed that expression of potential stem cell markers of the epidermis and HF was observed in the skin tumors of appendages and human basal cell carcinomas. 29 Also, they demonstrated that many of these markers appeared to be downregulated during tumor progression. These studies have expressed the importance of general HF markers in that it can change expression levels in some pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

Assessment of markers expressed in human hair follicles according to different skin regions

Yay¹,

Göktepe²,

Bahadir³

et al. 2018

Adv Clin Exp Med

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Expression of epidermal stem cell markers in skin and adnexal malignancies

Abstract: Expression of potential stem cell markers of the epidermis and hair follicles was observed in skin tumours of appendages and BCCs. However, during tumour progression, many of these markers seemed to be downregulated.

Cited by 25 publications

References 49 publications

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation

Neuroendocrinology and neurobiology of sebaceous glands

Assessment of markers expressed in human hair follicles according to different skin regions

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