Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells.

Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells.
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DOI:
10.1016/j.stem.2011.02.021
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发表时间:
2011-05-06
期刊:
影响因子:
23.9
通讯作者:
Joyner, Alexandra L.
Joyner, Alexandra L.
中科院分区:
医学1区
文献类型:
--
作者:
Brownell, Isaac;Guevara, Elizabeth;Bai, C. Brian;Loomis, Cynthia A.;Joyner, Alexandra L.

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在成年皮肤中,毛囊隆突部的干细胞周期性地使毛囊再生,而另一种不同的干细胞群则维持表皮。所有隆突细胞具有同等再生潜能的程度尚不清楚。我们发现,来自神经元的音猬因子(Shh)向处于休止期毛囊隆突中由刺猬反应基因Gli1标记的一群新细胞发出信号。表达Gli1的隆突细胞在其原生环境中作为多能干细胞发挥作用,并反复使生长期毛囊再生。对Shh有反应的神经周围隆突细胞参与愈合的皮肤伤口,值得注意的是,它们在伤口处可改变其谱系成为表皮干细胞。神经周围微环境(包括Shh)对于毛囊在急性伤口愈合和皮肤内稳态中的作用并非必需,但对于维持能够成为表皮干细胞的隆突细胞是必要的。因此,神经营造了一种微环境,在其中Shh造就了一群在分子和表型上都不同的毛囊干细胞。
In adult skin, stem cells in the hair follicle bulge cyclically regenerate the follicle, whereas a distinct stem cell population maintains the epidermis. The degree to which all bulge cells have equal regenerative potential is not known. We found that Sonic hedgehog (Shh) from neurons signals to a novel population of cells in the telogen bulge marked by the Hedgehog response gene Gli1. Gli1-expressing bulge cells function as multipotent stem cells in their native environment and repeatedly regenerate the anagen follicle. Shh-responding perineural bulge cells incorporate into healing skin wounds where, notably, they can change their lineage into epidermal stem cells. The perineural niche (including Shh) is dispensable for follicle contributions to acute wound healing and skin homeostasis, but is necessary to maintain bulge cells capable of becoming epidermal stem cells. Thus nerves cultivate a microenvironment where Shh creates a molecularly and phenotypically distinct population of hair follicle stem cells.
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