Xu Zijian, Wang Wenjie, Jiang Kaiju, Yu Zhou, Huang Huanwei, Wang Fengchao, Zhou Bin, Chen Ting
College of Biological Sciences, China Agricultural University, Beijing, China.
National Institute of Biological Sciences, Beijing, China.
Elife. 2015 Dec 14;4:e10567. doi: 10.7554/eLife.10567.
Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation.
长期存在的成体干细胞在生物体的整个生命周期中维持组织再生。据推测,它们起源于胚胎祖细胞,这些祖细胞在器官发生结束时获得长期自我更新能力和多能性。实现这一过程的机制往往仍不清楚。在这里,我们发现长期存在的毛囊干细胞起源于占据由减弱的Wnt/β-连环蛋白信号所定义的特定位置的胚胎祖细胞。毛囊起始以基板形成为标志,这依赖于Wnt/β-连环蛋白信号的激活。此后不久,毛囊上部会出现一个Wnt/β-连环蛋白信号减弱的区域。位于该区域的胚胎祖细胞获得成体干细胞标志物的表达,并在器官发生结束时成为确定的长期毛囊干细胞。Wnt/β-连环蛋白信号的减弱是毛囊干细胞特化的先决条件,因为它抑制了干细胞形成所需的Sox9。