College of Plant Science and Technology, Beijing University of Agriculture, No. 7 Beinong Road, Changping District, Beijing, 102206, China.
College of Life Sciences, Capital Normal University, Beijing, 100048, China.
Sci Rep. 2019 Apr 16;9(1):6118. doi: 10.1038/s41598-019-42630-y.
Stem cell competition could select the fittest stem cells and potentially control tumorigenesis. However, little is known about the underlying molecular mechanisms. Here, we find that ectopic Decapentaplegic (Dpp) signal activation by expressing a constitutively active form of Thickveins (Tkv) in cyst stem cells (CySCs) leads to competition between CySCs and germline stem cells (GSCs) for niche occupancy and GSC loss. GSCs are displaced from the niche and undergo differentiation. Interestingly, we find that induction of Tkv results in elevated expression of vein, which further activates Epidermal Growth Factor Receptor (EGFR) signaling in CySCs to promote their proliferation and compete GSCs out of the niche. Our findings elucidate the important role of Dpp signaling in regulating stem cell competition and tumorigenesis, which could be shed light on tumorigenesis and cancer treatment in mammals.
干细胞竞争可以选择最适合的干细胞，并可能控制肿瘤发生。然而，其潜在的分子机制知之甚少。在这里，我们发现通过在胞囊干细胞（CySCs）中表达组成型激活形式的 Thickveins（Tkv）来异位激活 Decapentaplegic（Dpp）信号，会导致 CySCs 和生殖干细胞（GSCs）争夺龛位占据和 GSC 损失的竞争。GSCs 从龛位中被置换并发生分化。有趣的是，我们发现诱导 Tkv 会导致 vein 的表达升高，这进一步激活 CySCs 中的表皮生长因子受体（EGFR）信号，促进其增殖并将 GSCs 挤出龛位。我们的发现阐明了 Dpp 信号在调节干细胞竞争和肿瘤发生中的重要作用，这可能为哺乳动物的肿瘤发生和癌症治疗提供启示。
