Vasculature atrophy causes a stiffened microenvironment that augments epidermal stem cell differentiation in aged skin

被引：20

作者：

Ichijo, Ryo ^{[1
]}

Maki, Koichiro ^{[2
]}

Kabata, Mio ^{[3
]}

Murata, Teruasa ^{[4
]}

Nagasaka, Arata ^{[5
]}

Ishihara, Seiichiro ^{[6
,7
]}

Haga, Hisashi ^{[6
,7
]}

Honda, Tetsuya ^{[8
]}

Adachi, Taiji ^{[2
,9
]}

Yamamoto, Takuya ^{[3
,10
,11
]}

Toyoshima, Fumiko ^{[1
,9
]}

机构：

[1] Kyoto Univ, Inst Life & Med Sci, Dept Biosyst Sci, Lab Tissue Homeostasis, Kyoto, Japan

[2] Kyoto Univ, Inst Life & Med Sci, Dept Biosyst Sci, Lab Biomech, Kyoto, Japan

[3] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Dept Life Sci Frontiers, Kyoto, Japan

[4] Kyoto Univ, Grad Sch Med, Dept Dermatol, Kyoto, Japan

[5] Meikai Univ, Div Anat, Sch Dent, Sakado, Japan

[6] Hokkaido Univ, Fac Adv Life Sci, Dept Adv Transdisciplinary Sci, Sapporo, Japan

[7] Hokkaido Univ, Soft Matter GI CoRE, Sapporo, Japan

[8] Hamamatsu Univ, Dept Dermatol, Sch Med, Hamamatsu, Japan

[9] Kyoto Univ, Grad Sch Biostudies, Dept Mammalian Regulatory Network, Kyoto, Japan

[10] Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Kyoto, Japan

[11] RIKEN, Med Risk Avoidance Based iPS Cells Team, Ctr Adv Intelligence Project AIP, Kyoto, Japan

来源：

NATURE AGING | 2022年 / 2卷 / 07期

关键词：

LONG PENTRAXIN PTX3; ANGIOGENESIS; NEURONS; PIEZO1; DAMAGE; WAVES; TOUCH; VEGF;

D O I：

10.1038/s43587-022-00244-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Stem cell loss causes tissue deterioration associated with aging. The accumulation of genomic and oxidative stress-induced DNA damage is an intrinsic cue for stem cell loss(1,2); however, whether there is an external microenvironmental cue that triggers stem cell loss remains unclear. Here we report that the involution of skin vasculature causes dermal stiffening that augments the differentiation and hemidesmosome fragility of interfollicular epidermal stem cells (IFESCs) in aged mouse skin. Aging-related IFESC dysregulation occurs in plantar and tail skin, and is correlated with prolonged calcium influx, which is contributed by the mechanoresponsive ion channel Piezo1 (ref. (3)). Epidermal deletion of Piezo1 ameliorated IFESC dysregulation in aged skin, whereas Piezo1 activation augmented IFESC differentiation and hemidesmosome fragility in young mice. The dermis stiffened with age, which was accompanied by dermal vasculature atrophy. Conversely, induction of the dermal vasculature softened the dermis and ameliorated IFESC dysregulation in aged skin. Single-cell RNA sequencing of dermal fibroblasts identified an aging-associated anti-angiogenetic secretory molecule, pentraxin 3 (ref. (4)), which caused dermal sclerotization and IFESC dysregulation in aged skin. Our findings show that the vasculature softens the microenvironment for stem cell maintenance and provide a potential mechanobiology-based therapeutic strategy against skin disorders in aging.

引用

页码：592 / +

页数：23

共 43 条

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