Human epithelial hair follicle stem cells and their progeny: Current state of knowledge, the widening gap in translational research and future challenges

Purba, Talveen S.; Haslam, Iain S.; Poblet, Enrique; Jiménez, Francisco; Gandarillas, Alberto; Izeta, Ander; Paus, Ralf

doi:10.1002/bies.201300166

Cited by 121 publications

(167 citation statements)

References 127 publications

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“…As outlined above, dogs and humans share some properties regarding their HC, the SC-associated biomarker expression pattern and hormonal responses. Purba et al (2014) have already summarized the major disadvantages of the murine model when studying human HF SCs. Our results may, in the future, also contribute to the understanding of human alopecia and skin cancer development, and our ongoing further investigations may help to find new therapeutic approaches for disorders associated with an impaired SC compartment.…”

Section: Discussionmentioning

confidence: 99%

Stem Cell-Associated Marker Expression in Canine Hair Follicles

Gerhards

Sayar

Origgi

et al. 2016

J Histochem Cytochem.

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SummaryFunctional hair follicle (HF) stem cells (SCs) are crucial to maintain the constant recurring growth of hair. In mice and humans, SC subpopulations with different biomarker expression profiles have been identified in discrete anatomic compartments of the HF. The rare studies investigating canine HF SCs have shown similarities in biomarker expression profiles to that of mouse and human SCs. The aim of our study was to broaden the current repertoire of SC-associated markers and their expression patterns in the dog. We combined analyses on the expression levels of CD34, K15, Sox9, CD200, Nestin, LGR5 and LGR6 in canine skin using RT-qPCR, the corresponding proteins in dog skin lysates, and their expression patterns in canine HFs using immunohistochemistry. Using validated antibodies, we were able to define the location of CD34, Sox9, Keratin15, LGR5 and Nestin in canine HFs and confirm that all tested biomarkers are expressed in canine skin. Our results show similarities between the expression profile of canine, human and mouse HF SC markers. This repertoire of biomarkers will allow us to conduct functional studies and investigate alterations in the canine SC compartment of different diseases, like alopecia or skin cancer with the possibility to extend relevant findings to human patients. (J Histochem Cytochem 64:190-204, 2016)

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Section: Discussionmentioning

confidence: 99%

Stem Cell-Associated Marker Expression in Canine Hair Follicles

Gerhards

Sayar

Origgi

et al. 2016

J Histochem Cytochem.

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“…The HF's upper, distal part can be separated into four compartments. The bulge region of the outer root sheath (ORS), the seat of HF epithelial stem cells (Purba et al 2014), the isthmus and the junctional zone (the regions below or around the insertion of the sebaceous gland duct, respectively), and the infundibulum, which extends from the entrance of the sebaceous duct to the HF ostium, the opening of the HF onto the skin surface (Fig. 1).…”

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confidence: 99%

Deciphering the functions of the hair follicle infundibulum in skin physiology and disease

Schneider¹,

Paus

2014

Cell Tissue Res

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The infundibulum is the funnel-shaped, uppermost epithelial segment of the hair follicle. Thus, as the infundibulum represents a major interface zone of mammalian skin epithelium with the environment and harbors a rich residential microflora, it is not surprising that this area is endowed with a specialized immune system and innate immune defenses. Clinically, the infundibulum is quite important, as it becomes prominently involved in many skin diseases such as acne, infundibular folliculitis and cysts, hidradenitis suppurativa, keratosis pilaris, Fox-Fordyce disease, and a subtype of basal cell carcinoma. Nevertheless, the biology of the infundibulum is only poorly understood, and it remains largely unknown how exactly the infundibulum contributes to skin disease, and how it might be targeted effectively for treating important skin diseases. Several recent studies in mouse models have identified new potential infundibular markers, shed light upon infundibular development and homeostasis, identified infundibular epithelial stem cells, and have implicated the infundibulum in the pathogenesis of additional skin disorders. These recent insights encourage one to systematically re-visit the biology and pathology of the infundibulum, one of the most important, yet least-studied frontiers in mammalian epithelial physiology.

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“…The reasons for the observed intriguing differences between the impact of the metabolically stable N 1 -MeSpd versus Spd on K15 and K19 expression are still unclear. Indeed, the functional significance of both markers for HF stem cell biology remains obscure, and these markers might demarcate different subsets of cells, with different functions in the HF epithelium [14]. It is hypothesized that K19?…”

Section: Discussionmentioning

confidence: 99%

N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

et al. 2015

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Spermidine (Spd), the prototypic polyamine, has been shown to be essential for hair follicle (HF) growth. However, Spd can be readily converted into other polyamines, and is physiologically unstable. Therefore, to assess its individual functions on HFs, we used the metabolically stable Spd analog N(1)-methylspermidine (N(1)-MeSpd). N(1)-MeSpd was confirmed to be a metabolically stable compound, with a half life of 90 h. 0.5 µM N(1)-MeSpd strongly prolonged anagen and decreased cell apoptosis in HFs in culture after 6 days, accompanied by specific stimulation of the expression of the epithelial stem cell-associated keratin, K15. N(1)-MeSpd also reduced lactate dehydrogenase activity in the culture supernatant, a parameter of cell death and cell lysis. N(1)-MeSpd diminished intracellular reactive oxygen species production in cultured keratinocytes, and reduced tumor necrosis factor-α, interleukin (IL)-1β and IL-6 gene and protein expression after lipopolysaccharide stimulation. This suggests that some effects of N(1)-MeSpd may be mediated by anti-oxidative and anti-inflammatory effects. These additional properties of N(1)-MeSpd could be clinically important for the treatment of inflammatory alopecias and inflammatory scalp diseases.

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Human epithelial hair follicle stem cells and their progeny: Current state of knowledge, the widening gap in translational research and future challenges

Cited by 121 publications

References 127 publications

Stem Cell-Associated Marker Expression in Canine Hair Follicles

Stem Cell-Associated Marker Expression in Canine Hair Follicles

Deciphering the functions of the hair follicle infundibulum in skin physiology and disease

N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

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