Adult stem cells must continuously fine‐tune their behavior to regenerate damaged organs and avoid tumors. While several signaling pathways are well known to regulate somatic stem cells, the underlying mechanisms remain largely unexplored. Here, we demonstrate a cell‐intrinsic role for the OvoL family transcription factor, Shavenbaby (Svb), in balancing self‐renewal and differentiation of Drosophila intestinal stem cells. We find that svb is a downstream target of Wnt and EGFR pathways, mediating their activity for stem cell survival and proliferation. This requires post‐translational processing of Svb into a transcriptional activator, whose upregulation induces tumor‐like stem cell hyperproliferation. In contrast, the unprocessed form of Svb acts as a repressor that imposes differentiation into enterocytes, and suppresses tumors induced by altered signaling. We show that the switch between Svb repressor and activator is triggered in response to systemic steroid hormone, which is produced by ovaries. Therefore, the Svb axis allows intrinsic integration of local signaling cues and inter‐organ communication to adjust stem cell proliferation versus differentiation, suggesting a broad role of OvoL/Svb in adult and cancer stem cells.

中文翻译：

---

OvoL/Shavenbaby 的类固醇依赖性开关控制肠道干细胞的自我更新与分化


成体干细胞必须不断调整其行为，以再生受损器官并避免肿瘤。虽然众所周知有几种信号通路可以调节成体干细胞，但其潜在机制在很大程度上仍未被探索。在这里，我们证明了 OvoL 家族转录因子 Shavenbaby (Svb) 在平衡果蝇肠道干细胞的自我更新和分化中的细胞内在作用。我们发现svb是 Wnt 和 EGFR 通路的下游靶标，介导它们对干细胞存活和增殖的活性。这需要将 Svb 翻译后加工成转录激活剂，其上调会诱导肿瘤样干细胞过度增殖。相比之下，未加工形式的 Svb 充当阻遏蛋白，强制分化为肠细胞，并抑制信号传导改变诱导的肿瘤。我们发现，Svb 抑制子和激活子之间的转换是响应卵巢产生的全身类固醇激素而触发的。因此，Svb 轴允许局部信号传导和器官间通讯的内在整合，以调整干细胞增殖与分化，这表明 OvoL/Svb 在成人和癌症干细胞中具有广泛的作用。