Homeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation.

Homeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation.
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稳态表皮干细胞自我更新是由局部分化驱动的。

DOI:
10.1016/j.stem.2018.09.005
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发表时间:
2018-11-01
期刊:
影响因子:
23.9
通讯作者:
Greco V
Greco V
中科院分区:
医学1区
文献类型:
--
作者:
Mesa KR;Kawaguchi K;Cockburn K;Gonzalez D;Boucher J;Xin T;Klein AM;Greco V

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成体组织的维持取决于常驻干细胞群的持续活性,但在稳态过程中调节干细胞自我更新的机制仍然很大程度上未知。使用成像和跟踪方法捕获活体小鼠大面积区域的所有表皮干细胞活性,我们发现自我更新与表皮分化局部协调,滞后时间为一到两天。在稳态和实验扰动中,我们发现单个干细胞的分化之后是直接相邻细胞的分裂,但反之则不然。最后,我们证明从干细胞区室退出足以驱动邻近的干细胞自我更新。总之,这些发现证实表皮干细胞的自我更新并不是体内平衡的基本驱动力。相反,它精确地适应组织需求并直接响应邻近细胞的分化。通过捕获小鼠表皮大片区域的所有干细胞活性,Mesa、Kawaguchi、Cockburn 及其同事报告说,干细胞的自我更新是由相邻细胞的分化诱导的。这项研究确定了驱动干细胞自我更新的生理因素,扩大了目前对表皮稳态和再生的理解。
Maintenance of adult tissues depends on sustained activity of resident stem cell populations, yet the mechanisms that regulate stem cell self-renewal during homeostasis remain largely unknown. Using an imaging and tracking approach that captures all epidermal stem cell activity in large regions of living mice, we show that self-renewal is locally coordinated with epidermal differentiation, with a lag time of one to two days. In both homeostasis and upon experimental perturbation, we find that differentiation of a single stem cell is followed by division of a direct neighbor, but not vice versa. Finally, we show that exit from the stem cell compartment is sufficient to drive neighboring stem cell self-renewal. Together, these findings establish that epidermal stem cell self-renewal is not the constitutive driver of homeostasis. Instead it is precisely tuned to tissue demand and responds directly to neighbor cell differentiation. By capturing all stem cell activity in large regions of mouse epidermis, Mesa, Kawaguchi, Cockburn and colleagues report that stem cell self-renewal is induced by the differentiation of neighbors. This study identifies the physiological factors that drive stem cell self-renewal, expanding the current understanding of epidermal homeostasis and regeneration.
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