Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore.
Sci Signal. 2010 Jul 27;3(132):ra57. doi: 10.1126/scisignal.2000740.
Maintenance of stem cells requires spatially restricted, niche-associated signals. In the Drosophila female germline stem cell (GSC) niche, Decapentaplegic (DPP) is the primary niche-associated factor and functions over a short range to promote GSC self-renewal rather than differentiation. Here, we show that the GSC lineage and, more specifically, the stem cells themselves participate in the spatial restriction of DPP function by activating epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) signaling in the surrounding somatic cells. EGFR-MAPK signaling in somatic cells repressed the expression of dally, which encodes a glypican required for DPP movement and stability. Consequently, only GSCs close to the DPP source (the somatic cells in the niche) showed high signal activation and were maintained as stem cells, whereas cystoblasts outside the niche showed low signal activation and initiated differentiation. Thus, our data reveal that the reciprocal crosstalk between the GSCs and the somatic cells defines the spatial limits of DPP action and therefore the extent of the GSC niche.
干细胞的维持需要空间限制的、与小生境相关的信号。在果蝇雌性生殖干细胞(GSC)小生境中,Decapentaplegic(DPP)是主要的小生境相关因子,其作用范围较短,促进 GSC 自我更新而不是分化。在这里,我们表明 GSC 谱系,更具体地说,干细胞本身通过在周围体细胞中激活表皮生长因子受体(EGFR)-丝裂原活化蛋白激酶(MAPK)信号来参与 DPP 功能的空间限制。体细胞中的 EGFR-MAPK 信号抑制了编码糖蛋白聚糖(dally)的表达,该糖蛋白聚糖是 DPP 运动和稳定性所必需的。因此,只有靠近 DPP 源(小生境中的体细胞)的 GSCs 显示出高信号激活并维持为干细胞,而小生境外的囊胚细胞显示出低信号激活并启动分化。因此,我们的数据表明,GSCs 和体细胞之间的相互交流定义了 DPP 作用的空间限制,从而定义了 GSC 小生境的范围。