Resting no more: re‐defining telogen, the maintenance stage of the hair growth cycle

The secondary hair germ (SHG)-a transitory structure in the lower portion of the mouse telogen hair follicle (HF)-is directly involved in anagen induction and eventual HF regrowth. Some crucial aspects of SHG functioning and ontogenetic relations with other HF parts, however, remain undefined. According to recent evidence (in contrast to previous bulge-centric views), the SHG is the primary target of anagen-inducing signalling and a source of both the outer root sheath (ORS) and ascending HF layers during the initial (morphogenetic) anagen subphase. The SHG is comprised of two functionally distinct cell populations. Its lower portion (originating from lower HF cells that survived catagen) forms all ascending HF layers, while the upper SHG (formed by bulge-derived cells) builds up the ORS. The predetermination of SHG cells to a specific morphogenetic fate contradicts their attribution to the "stem cell" category and supports SHG designation as a "germinative" or a "founder" cell population. The mechanisms of this predetermination driving transition of the SHG from "refractory" to the "competent" state during the telogen remain unknown. Functionally, the SHG serves as a barrier, protecting the quiescent bulge stem cell niche from the extensive follicular papilla/SHG signalling milieu. The formation of the SHG is a prerequisite for efficient "precommitment" of these cells and provides for easier sensing and a faster response to anagen-inducing signals. In general, the formation of the SHG is an evolutionary adaptation, which allowed the ancestors of modern Muridae to acquire a specific, highly synchronized pattern of hair cycling.

Section: The Priming (Predetermination) Of Shg Cellsmentioning

confidence: 99%

Functional anatomy of the hair follicle: The Secondary Hair Germ

Panteleyev

2018

“…Like other PPAR isoforms, PPAR‐γ is prominently expressed in the human pilosebaceous unit (PSU), which likely incorporates—besides the hair follicle (HF), SG and arrector pili muscle—also perifollicular adipocytes and the eccrine gland . In human HFs, PPAR‐γ is expressed during the active growth stage of the hair cycle (anagen) in inner and outer root sheath keratinocytes (IRS‐KCs and ORS‐KCs) and hair matrix keratinocytes, but also in the inductive fibroblasts of the HF’s dermal papilla (DP), the mesenchymal “command structure” of the HF (Figure ) . Among the many important recognized functions that PPAR‐γ‐mediated signalling has in the PSU (Table ), we shall explore in the following only the HF, with emphasis on human scalp HFs in health and disease.…”

Section: Overview: Ppar‐γ and The Human Pilosebaceous Unitmentioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

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Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

“…But how achievable is this really in clinical practice? Exogen requires the prior formation of a club HS that can subsequently be shed and thus that an anagen HF has involuted into a catagen HF and subsequently entered telogen . In order to manipulate the excretory function of HFs, it could be useful to promote human catagen/telogen development.…”

Section: Clinical Perspectivesmentioning

confidence: 99%

“…Not only forensic scientists, but even the lay public are now well aware of the fact that plucked or cut hair shafts (HS) provide excellent source material for measuring and even timing the past systemic exposure of the human body to drugs (including drugs of abuse) and various toxins, including environmental toxins and heavy metals . Yet, even experts rarely reflect how and why these molecules get into the HS in the first place—and what this tells us about fundamental characteristics of this fascinating, cyclically remodelled mini‐organ …”

Section: Introductionmentioning

confidence: 99%

Do hair follicles operate as primitive, multifocal kidney‐like excretory (mini‐) organs?

Carre

Suzuki

Paus

2020

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Besides their many other functions, hair shafts (HS) also are a repository for potentially noxious compounds. These are neutralized by their deposition within terminally differentiated, avital epithelial cells (trichocytes) that also facilitate the interaction of potential toxins with melanin, a toxin‐adsorbent biopolymer. Trichocytes are completely extruded via HS shedding during exogen, an actively controlled process. This underappreciated functional property of the human hair follicle (HF) makes it a bona fide excretory (mini‐) organ. Here, we ask whether the ca. 2 million HFs of the human integument operate in part as primitive, spatially dispersed kidney‐like excretory organs. Despite the many obvious differences between kidneys and HFs, this provocative hypothesis is also supported by other underappreciated renal‐follicular similarities such as anatomical parallels between Bowman's capsule and the anagen hair bulb, renal podocytes and HF winged cells ["Fuegelzellen"], and hypoxia‐dependent production of erythropoietin and extensive prostaglandin synthesis by human scalp HFs—just as in the kidney. The proposed kidney‐like excretory function of HFs may have constituted a major selection advantage of mammals during evolution and could be clinically relevant. We explain how the many open questions (eg, how are molecules destined to be excreted by hair shaft entrapment recognized, taken up and deposited into hair matrix cells?) can be tested experimentally. Finally, we explore how the therapeutic targeting of kidney‐like excretory HF functions may usefully complement classical nephrological therapy (dialysis) and ask whether stimulation of intrafollicular erythropoietin synthesis might become exploitable for the benefit of patients with renal anaemia.