Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
EMBO J. 2018 May 2;37(9). doi: 10.15252/embj.201798280. Epub 2018 Apr 3.
Tissues contain distinct stem cell niches, but whether cell turnover is coordinated between niches during growth is unknown. Here, we report that in mouse skin, hair growth is accompanied by sebaceous gland and interfollicular epidermis expansion. During hair growth, cells in the bulge and outer root sheath temporarily upregulate the glutamate transporter SLC1A3, and the number of SLC1A3 basal cells in interfollicular epidermis and sebaceous gland increases. Fate mapping of SLC1A3 cells in mice revealed transient expression in proliferating stem/progenitor cells in all three niches. Deletion of delays hair follicle anagen entry, uncouples interfollicular epidermis and sebaceous gland expansion from the hair cycle, and leads to reduced fur density in aged mice, indicating a role of SLC1A3 in stem/progenitor cell activation. Modulation of metabotropic glutamate receptor 5 activity mimics the effects of SLC1A3 deletion or inhibition. These data reveal that stem/progenitor cell activation is synchronized over distinct niches during growth and identify SLC1A3 as a general marker and effector of activated epithelial stem/progenitor cells throughout the skin.
组织中包含独特的干细胞龛，但在生长过程中龛之间的细胞更替是否协调尚不清楚。本文中，我们报道了在小鼠皮肤中，毛发的生长伴随着皮脂腺和毛囊间表皮的扩张。在毛发生长过程中，隆起部和外根鞘中的细胞暂时上调谷氨酸转运蛋白 SLC1A3，毛囊间表皮和皮脂腺中 SLC1A3 基底细胞的数量增加。通过对 SLC1A3 细胞的小鼠进行基因标记，发现在所有三个龛中，SLC1A3 都短暂表达在增殖性干细胞/祖细胞中。SLC1A3 缺失延迟了毛囊生长期的进入，使毛囊间表皮和皮脂腺的扩张与毛囊周期脱耦联，并导致老年小鼠的毛密度降低，表明 SLC1A3 在干细胞/祖细胞的激活中起作用。代谢型谷氨酸受体 5 活性的调节模拟了 SLC1A3 缺失或抑制的作用。这些数据表明，在生长过程中，干细胞/祖细胞的激活在不同的龛之间是同步的，并确定 SLC1A3 是整个皮肤中激活的上皮干细胞/祖细胞的通用标记物和效应物。
