Driskell Iwona, Oeztuerk-Winder Feride, Humphreys Peter, Frye Michaela
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Stem Cells. 2015 Mar;33(3):988-98. doi: 10.1002/stem.1910.
Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent.
成年哺乳动物的表皮含有多个干细胞群体,其中静止的和增殖性更强的干细胞及祖细胞群体共存。然而,这些群体在体内平衡中的精确相互关系仍不清楚。在这里,我们通过对维持成年皮肤所必需的关键组蛋白甲基转移酶Setd8进行基因消融,阻断了表达静止角蛋白19(K19)的毛囊隆突干细胞对毛囊形成的贡献。Setd8的缺失通过抑制细胞分裂和诱导细胞死亡,消除了隆突细胞对毛囊再生的贡献,但毛囊的生长和形态未受影响。此外,毛囊隆突中Setd8的消融阻断了K19阳性干细胞对受伤表皮的贡献,但伤口愈合过程未改变。我们的数据表明,静止的隆突干细胞在短期内对毛囊再生和表皮损伤并非必需,并支持静止和循环干细胞群体具有同等潜能的假说。