Data from: Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration

Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration.当组织发生损伤时，干细胞分裂会被激活以启动再生过程。目前学界对再生结束后干细胞有丝分裂活性如何被精准抑制的分子机制尚不完全明晰。本研究表明，硫酸乙酰肝素（heparan sulfate）的一种特异性修饰，在果蝇肠道干细胞（ISC）的正常中肠稳态维持与再生过程的分裂调控中发挥关键作用。细胞外硫酸乙酰肝素内切硫酸酯酶Sulf1的缺失，会导致正常稳态下ISC分裂水平升高，这一现象由JAK-STAT、表皮生长因子受体（EGFR）以及刺猬（Hedgehog）等促有丝分裂信号通路的上调所介导。通过构建再生模型，我们发现Sulf1突变体中的ISC无法在再生终止阶段正常停止分裂，证实Sulf1是再生结束后终止ISC分裂的必需因子。我们据此提出，借助硫酸乙酰肝素的结构修饰对促有丝分裂信号实施转录后调控，为再生过程中干细胞活性的精准时序调控提供了全新的调控途径。