Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue

Poblet, Enrique; Jiménez, Francisco; Escario-Travesedo, E.; Hardman, Jonathan A.; Hernández-Hernández, I.; Agudo-Mena, José Luis; Cabrera-Galván, Juan Jose; Nicu, Carina; Paus, Ralf

doi:10.1111/bjd.16436

Cited by 41 publications

(30 citation statements)

References 51 publications

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“…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. [58] 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), [59] the mesenchymal "command structure" of the HF (Figure 2). [60][61][62][63] Among the many important recognized functions that PPAR-γ-mediated signalling has in the PSU (Table 1), we shall explore in the following only the HF, with emphasis on human scalp HFs in health and disease.…”

Section: Overvie W: Pparγ and The H Uman Pilos Ebaceous Unitmentioning

confidence: 99%

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

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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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.

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Section: Overvie W: Pparγ and The H Uman Pilos Ebaceous Unitmentioning

confidence: 99%

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

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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“…Although autophagy has been linked to lipodystrophy in adipocytes differentiated from murine embryonic fibroblasts and in human skin fibroblasts, previous research has failed to consider lipophagy as a possible mechanism within mature DAs. In this context, it may be productive to examine DAs surrounding human hair follicles (HFs), including the stem cell–rich bulge area . While DAs undergo size oscillations during synchronized murine HF cycling, being larger in anagen, it remains unknown whether human DAs undergo changes in cell size during the anagen‐catagen transition.…”

Section: Premisesmentioning

confidence: 99%

Do human dermal adipocytes switch from lipogenesis in anagen to lipophagy and lipolysis during catagen in the human hair cycle?

Nicu

Hardman

Pople

et al. 2019

Experimental Dermatology

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In murine skin, dermal white adipose tissue (DWAT) undergoes fluctuations in size across the hair cycle, whereas changes in size, function and metabolism of dermal adipocytes (DAs) during the human scalp hair cycle remain unexplored. Transmission electron microscopy results suggest that during anagen‐catagen transition, human DAs co‐opt the autophagy machinery to undergo lipophagy within their lipid droplets. Whole‐mount staining of hair follicles (HFs) and surrounding DWAT for the autophagy marker LC3B confirms the increased presence of LC3B+ lipid droplets adjacent to catagen HFs; moreover, DWAT around catagen HFs engages in greater glycerol release compared to DWAT surrounding anagen HFs. Thus, we hypothesize that human DAs switch from lipogenesis during anagen to lipophagy together with lipolysis during catagen. We propose various experiments to further prove this hypothesis, whose systematic exploration should help to better characterize the functions of human DWAT and its communication with the HF.

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“…EU was found to be incorporated into cells of all human HF compartments, including the outer root sheath (ORS), hair matrix keratinocytes (MKs), the connective tissue sheath and dermal papilla (DP), as well in the sweat gland, newly recognized as being integral to the pilosebaceous unit [7] (Figure 1A). Interestingly, intrafollicular RNA synthesis differed between defined anatomical HF compartments.…”

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confidence: 99%

Visualization of Global RNA Synthesis in a Human (mini-) Organ in Situ by Click Chemistry

et al. 2018

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RNA synthesis can be detected by 5-ethynyl uridine (EU) incorporation and click chemistry. Despite identifying a fundamental functional process, this technique has yet to be widely applied to complex human tissue systems. By incorporating EU into human hair follicle (HF) organs cultured ex vivo, nascent RNA synthesis was detected in situ. EU differentially incorporated across the HF epithelium. Interestingly, RNA synthesis did not correlate with protein synthesis, proliferation or epithelial progenitor cell marker expression. By treating human HFs with the cytotoxic cell cycle inhibitor (R)-CR8, which inhibits transcriptional regulators CDK7 and CDK9, it was further shown that this technique can be used to sensitively detect changes in global RNA synthesis in situ. Together, this work delineates new insights into nascent RNA synthesis within a human (mini)- organ and describes a novel read-out parameter that will enrich future ex vivo human tissue research studies.

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Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue

Cited by 41 publications

References 51 publications

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

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

Do human dermal adipocytes switch from lipogenesis in anagen to lipophagy and lipolysis during catagen in the human hair cycle?

Visualization of Global RNA Synthesis in a Human (mini-) Organ in Situ by Click Chemistry

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