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皮质酮通过抑制GAS6控制毛囊干细胞的静息状态
2021-04-02 21:07

美国哈佛大学Ya-Chieh Hsu团队的研究发现皮质酮通过抑制GAS6控制毛囊干细胞的静息状态。相关论文在线发表在2021年3月31日出版的《自然》杂志上。

研究人员发现由肾上腺分泌的应激激素皮质酮调节小鼠毛囊干细胞(HFSC)的静止状态和毛发生长,啮齿类动物体内的皮质酮与人类皮质醇等效。在全身性皮质酮缺乏情况下,HFSCs在整个生命过程中都会进入多轮再生周期。相反,在长期处于压力条件下,皮质酮水平升高会延长HFSC的休眠期,并使毛囊处于延长的静止期。

从机制上讲,皮质酮作用于真皮乳头以抑制Gas6的表达,Gas6编码特异的分泌生长停滞因子。恢复Gas6的表达克服了压力诱导的HFSC活化和头发生长的抑制作用。该工作通过皮质酮对小生境的作用确定其是HFSC活化的系统性抑制因子,并证明消除这种抑制作用会使HFSCs进入频繁的再生周期,但不产生长期明显的缺陷。

据悉,长期持续处于压力环境可极大地影响组织的动态平衡,但是尚不清楚这些变化发生的机制。

附:英文原文

Title: Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence

Author: Sekyu Choi, Bing Zhang, Sai Ma, Meryem Gonzalez-Celeiro, Daniel Stein, Xin Jin, Seung Tea Kim, Yuan-Lin Kang, Antoine Besnard, Amelie Rezza, Laura Grisanti, Jason D. Buenrostro, Michael Rendl, Matthias Nahrendorf, Amar Sahay, Ya-Chieh Hsu

Issue&Volume: 2021-03-31

Abstract: Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we report that the stress hormone corticosterone—which is derived from the adrenal gland and is the rodent equivalent of cortisol in humans—regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice. In the absence of systemic corticosterone, HFSCs enter substantially more rounds of the regeneration cycle throughout life. Conversely, under chronic stress, increased levels of corticosterone prolong HFSC quiescence and maintain hair follicles in an extended resting phase. Mechanistically, corticosterone acts on the dermal papillae to suppress the expression of Gas6, a gene that encodes the secreted factor growth arrest specific 6. Restoring Gas6 expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Our work identifies corticosterone as a systemic inhibitor of HFSC activity through its effect on the niche, and demonstrates that the removal of such inhibition drives HFSCs into frequent regeneration cycles, with no observable defects in the long-term.

DOI: 10.1038/s41586-021-03417-2

Source: https://www.nature.com/articles/s41586-021-03417-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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