Department of Developmental Biology, Howard Hughes Medical Institute (HHMI), Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
Science. 2013 Dec 6;342(6163):1226-30. doi: 10.1126/science.1239730.
The skin is a classical example of a tissue maintained by stem cells. However, the identity of the stem cells that maintain the interfollicular epidermis and the source of the signals that control their activity remain unclear. Using mouse lineage tracing and quantitative clonal analyses, we showed that the Wnt target gene Axin2 marks interfollicular epidermal stem cells. These Axin2-expressing cells constitute the majority of the basal epidermal layer, compete neutrally, and require Wnt/β-catenin signaling to proliferate. The same cells contribute robustly to wound healing, with no requirement for a quiescent stem cell subpopulation. By means of double-labeling RNA in situ hybridization in mice, we showed that the Axin2-expressing cells themselves produce Wnt signals as well as long-range secreted Wnt inhibitors, suggesting an autocrine mechanism of stem cell self-renewal.
皮肤是一种由干细胞维持的经典组织。然而，维持毛囊间表皮的干细胞的身份及其控制其活性的信号源仍不清楚。通过对小鼠谱系追踪和定量克隆分析，我们发现 Wnt 靶基因 Axin2 标记了毛囊间表皮干细胞。这些表达 Axin2 的细胞构成了大部分基底层表皮细胞，它们处于中性竞争状态，并且需要 Wnt/β-连环蛋白信号来增殖。相同的细胞对创伤愈合有很大的贡献，而不需要静止的干细胞亚群。通过对小鼠进行双标记 RNA 原位杂交，我们发现表达 Axin2 的细胞本身既能产生 Wnt 信号，也能产生长距离分泌的 Wnt 抑制剂，这表明干细胞自我更新存在自分泌机制。
