Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

Matsumura, Hiroyuki; Mohri, Yasuaki; Morinaga, Hironobu; Fukuda, Makoto; Kurata, Sotaro; Nishimura, Emi K.

doi:10.1016/j.jdermsci.2017.02.156

Cited by 73 publications

(142 citation statements)

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“…We also found that the number of KRT15‐positive cells decreased with age (Fig. c), consistent with a previous report showing a decrease in HFSC with age …”

Section: Resultssupporting

confidence: 92%

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Extracellular proteoglycan decorin maintains human hair follicle stem cells

Miyachi¹,

Yamada

Kawagishi‐Hotta

et al. 2018

The Journal of Dermatology

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Hair follicle stem cells (HFSC) are localized in the bulge region of the hair follicle and play a role in producing hair. Recently, it has been shown that the number of HFSC decreases with age, which is thought to be a cause of senile alopecia. Therefore, maintaining HFSC may be key for the prevention of age‐related hair loss, but the regulatory mechanisms of HFSC and the effects of aging on them are largely unknown. In general, stem cells are known to require regulatory factors in the pericellular microenvironment, termed the stem cell niche, to maintain their cell function. In this study, we focused on the extracellular matrix proteoglycan decorin (DCN) as a candidate factor for maintaining the human HFSC niche. Gene expression analysis showed that DCN was highly expressed in the bulge region. We observed decreases in DCN expression as well as the number of KRT15‐positive HFSC with age. In vitro experiments with human plucked hair‐derived HFSC revealed that HFSC lost their undifferentiated state with increasing passages, and prior to this change a decrease in DCN expression was observed. Furthermore, knockdown of DCN promoted HFSC differentiation. In contrast, when HFSC were cultured on DCN‐coated plates, they showed an even more undifferentiated state. From these results, as a novel mechanism for maintaining HFSC, it was suggested that DCN functions as a stem cell niche component, and that the deficit of HFSC maintenance caused by a reduction in DCN expression could be a cause of age‐related hair loss.

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“…We also found that the number of KRT15‐positive cells decreased with age (Fig. c), consistent with a previous report showing a decrease in HFSC with age …”

Section: Resultssupporting

confidence: 92%

“…a,b). In addition, gene expression analysis showed that KRT15 and other HFSC markers, such as SOX9 and LRIG1 , were highly expressed in the primary culture (P0) and their expression decreased as the number of passages increased. In contrast, the expression of a differentiation marker IVL increased during culture.…”

Section: Resultsmentioning

confidence: 99%

Extracellular proteoglycan decorin maintains human hair follicle stem cells

Miyachi¹,

Yamada

Kawagishi‐Hotta

et al. 2018

The Journal of Dermatology

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“…In the skin, the proliferative capacity of hair follicle stem cells diminishes, as does their capacity for hair regeneration (Matsumura et al, 2016; Doles et al, 2012). Notably, blocking the inflammatory response is sufficient to reverse the proliferative defects in these stem cells.…”

Section: Introductionmentioning

confidence: 99%

Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease

Naik

Larsen

Cowley

et al. 2018

Cell

205

144

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Summary Stem cells regenerate tissues in homeostasis and under stress. By taking cues from their microenvironment or “niche”, they smoothly transition between these states. Immune cells have surfaced as prominent members of stem cell niches across the body. Here, we draw parallels between different stem cell niches to explore the context-specific interactions that stem cells have with tissue resident and recruited immune cells. We also highlight stem cells’ innate ability to sense and respond to stress, and the enduring memory that forms from such encounters. This fascinating crosstalk holds great promise for novel therapies in inflammatory diseases and regenerative medicine.

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“…Although their depletion convey in HF loss, in the most common pathological hair loss conditions, that is, alopecia areata (AA) and androgenic alopecia (AGA), HFSCs are preserved (but not DP cells) . In contrast, aging‐driven loss of hair regenerative capacity is associated with terminal differentiation and transepidermal clearance of HFSCs . Thus, from an in vitro tissue engineering perspective, mimicking in vivo contribution of both HFSC and DP seems critical to establish a successful HF regeneration strategy.…”

Section: Hf Bioengineering: Cell Sources and Challengesmentioning

confidence: 99%

Tissue engineering strategies for human hair follicle regeneration: How far from a hairy goal?

Castro

Logarinho

2019

Stem Cells Translational Medicine

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The demand for an efficient therapy for alopecia disease has fueled the hair research field in recent decades. However, despite significant improvements in the knowledge of key processes of hair follicle biology such as genesis and cycling, translation into hair follicle replacement therapies has not occurred. Great expectation has been recently put on hair follicle bioengineering, which is based on the development of fully functional hair follicles with cycling activity from an expanded population of hair‐inductive (trichogenic) cells. Most bioengineering approaches focus on in vitro reconstruction of folliculogenesis by manipulating key regulatory molecular/physical features of hair follicle growth/cycling in vivo. Despite their great potential, no cell‐based product is clinically available for hair regeneration therapy to date. This is mainly due to demanding issues that still hinder the functionality of cultured human hair cells. The present review comprehensively compares emergent strategies using different cell sources and tissue engineering approaches, aiming to successfully achieve a clinical cure for hair loss. The hurdles of these strategies are discussed, as well as the future directions to overcome the obstacles and fulfill the promise of a “hairy” feat.

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Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

Cited by 73 publications

References 0 publications

Extracellular proteoglycan decorin maintains human hair follicle stem cells

Extracellular proteoglycan decorin maintains human hair follicle stem cells

Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease

Tissue engineering strategies for human hair follicle regeneration: How far from a hairy goal?

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