Fly stocks used in this work.

Tissue maintenance is underpinned by resident stem cells whose activity is modulated by microenvironmental cues. Using Drosophila as a simple model to identify regulators of stem cell behaviour and survival in vivo, we have identified novel connections between the conserved transmembrane proteoglycan Syndecan, nuclear properties and stem cell function. In the Drosophila midgut, Syndecan depletion in intestinal stem cells results in their loss from the tissue, impairing tissue renewal. At the cellular level, Syndecan depletion alters cell and nuclear shape, and causes nuclear lamina invaginations and DNA damage. In a second tissue, the developing Drosophila brain, live imaging revealed that Syndecan depletion in neural stem cells results in nuclear envelope remodelling defects which arise upon cell division. Our findings reveal a new role for Syndecan in the maintenance of nuclear properties in diverse stem cell types.

组织维持依赖于定居干细胞（resident stem cells），其活性受微环境信号（microenvironmental cues）调控。本研究以果蝇（Drosophila）为简化模型，在体内鉴定干细胞行为与存活的调控因子，最终发现了保守型跨膜蛋白聚糖黏结蛋白聚糖（Syndecan）、细胞核特性与干细胞功能之间的全新关联。在果蝇中肠中，肠道干细胞内的黏结蛋白聚糖耗竭会导致干细胞从组织中丢失，损害组织更新能力。在细胞层面，黏结蛋白聚糖耗竭会改变细胞与细胞核形态，并引发核纤层（nuclear lamina）内陷与DNA损伤（DNA damage）。在另一研究组织——发育中的果蝇脑中，活细胞成像（live imaging）显示，神经干细胞（neural stem cells）内的黏结蛋白聚糖耗竭会导致细胞分裂过程中出现核被膜重塑（nuclear envelope remodelling）缺陷。本研究结果揭示了黏结蛋白聚糖在多种干细胞类型的细胞核特性维持中的全新功能。