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Abstract：
Most hematological malignancies are associated with reduced expression of one or more components of the Endosomal Sorting Complex Required for Transport (ESCRT). However, the roles of ESCRT in stem cell and progenitor maintenance are not resolved. Parsing signaling pathways in relation to the canonical role of ESCRT poses a challenge. The Drosophila hematopoietic organ, the larval lymph gland, provides a path to dissect the roles of cellular trafficking pathways such as ESCRT in blood development and maintenance. Drosophila has 13 core ESCRT components. Knockdown of individual ESCRTs showed that only Vps28 and Vp36 were required in all lymph gland progenitors. Using the well-conserved ESCRT-II complex as an example of the range of phenotypes seen upon ESCRT depletion, we show that ESCRTs have cell-autonomous as well as non-autonomous roles in progenitor maintenance and differentiation. ESCRT depletion also sensitized posterior lobe progenitors to respond to immunogenic wasp infestation. We also identify key heterotypic roles for ESCRT in position-dependent control of Notch activation to suppress crystal cell differentiation. Our study shows that the cargo sorting machinery determines the identity of progenitors and their adaptability to the dynamic microenvironment. These mechanisms for control of cell fate may tailor developmental diversity in multiple contexts.
摘要：
大多数血液恶性肿瘤与转运所需的内体分选复合物（ESCRT）的一种或多种成分的表达降低有关。然而,ESCRT在干细胞和祖细胞维持中的作用尚未解决。解析与ESCRT的规范作用相关的信号通路提出了挑战。果蝇的造血器官,幼虫的淋巴腺，提供了一条途径来剖析细胞运输途径如ESCRT在血液发育和维持中的作用。果蝇有13个核心ESCRT组件。单个ESCRT的敲除表明，所有淋巴腺祖细胞仅需要Vps28和Vp36。使用保存良好的ESCRT-II复合物作为ESCRT耗尽后观察到的表型范围的示例，我们表明ESCRT在祖细胞维持和分化中具有细胞自主和非自主作用。ESCRT耗竭还使后叶祖细胞对免疫原性黄蜂侵染作出反应。我们还确定了ESCRT在Notch激活的位置依赖性控制以抑制晶体细胞分化中的关键异型作用。我们的研究表明，货物分拣机械决定了祖细胞的身份及其对动态微环境的适应性。这些控制细胞命运的机制可以在多种情况下调整发育多样性。
