Jaks Viljar, Barker Nick, Kasper Maria, van Es Johan H, Snippert Hugo J, Clevers Hans, Toftgård Rune
Karolinska Institutet, Department of Biosciences and Nutrition, Novum, SE-141 57 Huddinge, Sweden.
Nat Genet. 2008 Nov;40(11):1291-9. doi: 10.1038/ng.239. Epub 2008 Oct 12.
In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair follicles and in the lower outer root sheath of anagen hair follicles. Here we show that Lgr5(+) cells comprise an actively proliferating and multipotent stem cell population able to give rise to new hair follicles and maintain all cell lineages of the hair follicle over long periods of time. Lgr5(+) progeny repopulate other stem cell compartments in the hair follicle, supporting the existence of a stem or progenitor cell hierarchy. By marking Lgr5(+) cells during trafficking through the lower outer root sheath, we show that these cells retain stem cell properties and contribute to hair follicle growth during the next anagen. Expression analysis suggests involvement of autocrine Hedgehog signaling in maintaining the Lgr5(+) stem cell population.
在小鼠毛囊中，隆突部位的一群静止细胞被认为具有干细胞活性。肠道干细胞标志物Lgr5在休止期毛囊的隆突和次级毛芽中处于活跃循环的细胞以及生长期毛囊的外根鞘下部表达。我们在此表明，Lgr5(+)细胞构成了一个活跃增殖且具有多能性的干细胞群体，能够产生新的毛囊，并在很长一段时间内维持毛囊的所有细胞谱系。Lgr5(+)子代重新填充毛囊中的其他干细胞区室，支持了干细胞或祖细胞层级结构的存在。通过在Lgr5(+)细胞穿过外根鞘下部的过程中对其进行标记，我们发现这些细胞保留了干细胞特性，并在接下来的生长期对毛囊生长有贡献。表达分析表明自分泌的Hedgehog信号传导参与维持Lgr5(+)干细胞群体。
