Mapping the expression of epithelial hair follicle stem cell‐related transcription factors <scp>LHX</scp>2 and <scp>SOX</scp>9 in the human hair follicle

Purba, Talveen S.; Haslam, Iain S.; Shahmalak, Asim; Bhogal, Ranjit; Paus, Ralf

doi:10.1111/exd.12700

Cited by 32 publications

(46 citation statements)

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“…In this study we confirm our hypothesis that the association of the secretory portion of ESGs with the PSU is a common finding, at least in human scalp skin, and document that the ESG coil lies in close proximity to the progenitor‐cell‐rich sub‐bulge region of the HF epithelium and its surrounding connective tissue sheath. Given the high density of ESGs in human scalp skin, one may wonder whether it is a mere consequence of tighter skin appendage packaging and spacing meaning that many HFs are in close proximity to ESGs.…”

Section: Discussionsupporting

confidence: 88%

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

et al. 2018

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We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term 'adnexal skin unit'. The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration and repair and in selected skin diseases.

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Section: Discussionsupporting

confidence: 88%

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

et al. 2018

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“…We found that treatment of hair follicles with paclitaxel or docetaxel significantly increased the number of cleaved caspase-3 + and pH3 + cells in the outer root sheath (Appendix Fig S1G-K). Dual immunofluorescence staining for cleaved caspase-3 or pH3, alongside the hair follicle epithelial stem/progenitor cell marker keratin 15 (K15) (Cotsarelis, 2006;Purba et al, 2014) in paclitaxel-treated hair follicles, showed that accumulating cleaved caspase-3 + and pH3 + cells localise within and immediately adjacent to K15 + expressing cells of the bulge stem cell region and proximal bulb outer root sheath progenitor compartment (Fig 4Ai-ii) (Purba et al, 2014(Purba et al, , 2015. An analysis of the number of cleaved caspase-3 + cells following extended human hair follicle organ cultures (see Materials and Methods) revealed that paclitaxel significantly increases apoptosis in the K15 + bulge (Fig 4B and C).…”

Section: Taxanes Promote Micronucleation Transcriptional Arrest and mentioning

confidence: 99%

CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane‐induced alopecia

et al. 2019

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Taxanes are a leading cause of severe and often permanent chemotherapy‐induced alopecia. As the underlying pathobiology of taxane chemotherapy‐induced alopecia remains poorly understood, we investigated how paclitaxel and docetaxel damage human scalp hair follicles in a clinically relevant ex vivo organ culture model. Paclitaxel and docetaxel induced massive mitotic defects and apoptosis in transit amplifying hair matrix keratinocytes and within epithelial stem/progenitor cell‐rich outer root sheath compartments, including within Keratin 15+ cell populations, thus implicating direct damage to stem/progenitor cells as an explanation for the severity and permanence of taxane chemotherapy‐induced alopecia. Moreover, by administering the CDK4/6 inhibitor palbociclib, we show that transit amplifying and stem/progenitor cells can be protected from paclitaxel cytotoxicity through G1 arrest, without premature catagen induction and additional hair follicle damage. Thus, the current study elucidates the pathobiology of taxane chemotherapy‐induced alopecia, highlights the paramount importance of epithelial stem/progenitor cell‐protective therapy in taxane‐based oncotherapy, and provides preclinical proof‐of‐principle in a healthy human (mini‐) organ that G1 arrest therapy can limit taxane‐induced tissue damage.

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“…Human HF organ culture or xenotransplantation (,s6) permits the in situ manipulation of a complex human (mini‐)organ under clinically relevant conditions. By utilizing this accessible human tissue and cell interaction system, one can study the function of distinct keratinocyte populations of human adult epithelial progenitor cells , their differentiated keratinocyte (KC) progeny and how they can interact within the HF microenvironment (i.e. hair matrix‐KCs, outer root sheath‐KCs, inner root sheath‐KCs, companion layer KCs as well as KCs of the hair shaft cortex, medulla and cuticle) .…”

Section: Why Human Hf Cell Cycle Dynamics Are Biologically and Clinicmentioning

confidence: 99%

A primer for studying cell cycle dynamics of the human hair follicle

Purba

Brunken

Hawkshaw

et al. 2016

Experimental Dermatology

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Abstract:The cell cycle is of major importance to human hair follicle (HF) biology. Not only is continuously active cell cycling required to facilitate healthy hair growth in anagen VI HFs, but perturbations in the cell cycle are likely to be of significance in HF pathology (i.e. in scarring, non-scarring, chemotherapy-induced and androgenic alopecias). However, cell cycle dynamics of the human hair follicle (HF) are poorly understood in contrast to what is known in mouse. The current Methods Review aims at helping to close this gap by presenting a primer that introduces immunohistological/immunofluorescent techniques to study the cell cycle in the human HF. Moreover, this primer encourages the exploitation of the human HF as a powerful and clinically relevant tool to investigate mammalian cell cycle biology in situ. To achieve this, we describe methods to study markers of general 'proliferation' (nuclei count, Ki-67 expression), apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labelling, cleaved caspase 3), mitosis (phospho-histone H3, 'pS780'), DNA synthesis (5-ethynyl-2 0 -deoxyuridine) and cell cycle regulation (cyclins) in the human HF. In addition, we provide specific examples of dual immunolabelling for instructive cell cycle analyses and for investigating the cell cycle behaviour of specific HF keratinocyte subpopulations, such as keratin 15+ stem/ progenitor cells.

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Mapping the expression of epithelial hair follicle stem cell‐related transcription factors LHX2 and SOX9 in the human hair follicle

Cited by 32 publications

References 50 publications

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

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

CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane‐induced alopecia

A primer for studying cell cycle dynamics of the human hair follicle

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