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

Matsumura, Hiroyuki; Mohri, Yasuaki; Bình, Nguyễn Thanh; Morinaga, Hironobu; Fukuda, Makoto; Ito, Mayumi; Kurata, Sotaro; Hoeijmakers, Jan H.J.; Nishimura, Emi K.

doi:10.1126/science.aad4395

Cited by 291 publications

(202 citation statements)

References 70 publications

(71 reference statements)

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“…The mechanism for this switch is unknown. It was proposed that stem cell characteristics are provided by the cell environment as opposed to endogenous cell properties (Rompolas et al 2013), and that damage to their niche depletes the hair follicle stem cell population (Matsumura et al 2016). This interesting possibility could have important implications for cutaneous wound healing since damage to the extracellular matrix is a hallmark of skin aging (Rittié and Fisher 2015).…”

Section: Stem Cell Response To Woundingmentioning

confidence: 99%

Cellular mechanisms of skin repair in humans and other mammals

Rittié

2016

J. Cell Commun. Signal.

238

167

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The increased incidence of non-healing skin wounds in developed societies has prompted tremendous research efforts on the complex process known as Bwound healing^. Unfortunately, the weak relevance of modern wound healing research to human health continues to be a matter of concern. This review summarizes the current knowledge of the cellular mechanisms that mediate wound closure in the skin of humans and laboratory animals. The author highlights the anatomical singularities of human skin vs. the skin of other mammals commonly used for wound healing research (i.e. as mice, rats, rabbits, and pigs), and discusses the roles of stem cells, myofibroblasts, and the matrix environment in the repair process. The majority of this review focuses on reepithelialization and wound closure. Other aspects of wound healing (e.g. inflammation, fibrous healing) are referred to when relevant to the main topic. This review aims at providing the reader with a clear understanding of the similarities and differences that have been reported over the past 100 years between the healing of human wounds and that of other mammals.

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Section: Stem Cell Response To Woundingmentioning

confidence: 99%

Cellular mechanisms of skin repair in humans and other mammals

Rittié

2016

J. Cell Commun. Signal.

238

167

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“…Importantly, aged HFSCs lose their stem cell signature and commit to epidermal differentiation, and they are finally eliminated from the epidermis [68]. The progressive depletion of HFSCs and the cell fate change observed in aPKC cKO mice are similar to aged mice.…”

Section: Apkc and Agingmentioning

confidence: 90%

“…A recent study clarified that accumulation of DNA damage in HFSCs leads to proteolysis of COL17A1 that triggers HFSC aging [68]. Importantly, aged HFSCs lose their stem cell signature and commit to epidermal differentiation, and they are finally eliminated from the epidermis [68].…”

Section: Apkc and Agingmentioning

confidence: 99%

Mechanism of Hair Loss from the Point of View of Epidermal Cell Polarity

Osada¹

2017

Hair and Scalp Disorders

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The epidermis and hair follicle epithelium have a polarized stratified architecture, and epidermal homeostasis is maintained by stem cell and progenitor populations present in the basal layer of the interfollicular epidermis and in different compartments of the hair follicle. Atypical protein kinase Cs (aPKCs-a subgroup of the PKC family) are localized to tight junctions and regulate the apico-basal epithelial polarity in simple epithelia. In the stratified epidermis, aPKCs are expressed in the basal layer and are implicated in the regulation of oriented cell division by localizing to the apical pole of basal cells during mitosis. Mutant mice harboring epidermis-specific deletion of aPKCλ showed progressive hair loss, abnormal hair cycling, an increase of asymmetric cell division in the epidermis and hair follicles, and a gradual decrease in the hair follicle stem cell (HFSC) population. Lineage tracing analysis has demonstrated that mutant HFSCs lose their stemness and become more committed proliferating progenitors. Moreover, the expressions of quiescence-inducing factors (Bmp6 and Fgf18) were suppressed in the mutant hair follicles. These results clarify a novel function of aPKCλ in maintaining the quiescence of HFSCs and suggest that epidermal cell polarity is a new clue to understanding the pathogenesis of hair loss.

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“…Matsumura et al [11] described the morphological changes in the mouse HF with aging. As the mouse aged, hair loss occurred and histologically there was HF miniaturization and a decrease in numbers of HFs.…”

Section: B) Agingmentioning

confidence: 99%

“…Matsumura et al [11] explored some of the mechanisms involved in this cell fate decision. Aged HFSCs showed evidence of more accumulated unrepaired DNA damage than young HFSCs.…”

Section: B) Agingmentioning

confidence: 99%

Stem cells and Aging

Singer

2016

Stem Cell Transl Investig

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The prevailing view of the aging process is that it reflects the integrated sequelae of accumulated random biological damage. These sequelae have been referred to as the hallmarks of aging and one of these hallmarks is the age-related decline in somatic stem cell functions; termed stem cell exhaustion. This stem cell exhaustion construct implies that stem cell aging across different tissues should have a number of similar characteristics. However, such is not the case. The characteristics of aging for stem cell populations in a variety of tissues, (hair follicle, skeletal muscle, hematopoietic tissue, skin, intestine and testes), display many distinctive tissue specific features. This observation implies that stem cell exhaustion is not a generic process consequent to the accumulation of random biological damage but rather represents the manifestation of tissue specific evolved programs.

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

Cited by 291 publications

References 70 publications

Cellular mechanisms of skin repair in humans and other mammals

Cellular mechanisms of skin repair in humans and other mammals

Mechanism of Hair Loss from the Point of View of Epidermal Cell Polarity

Stem cells and Aging

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