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 (HS) is critical in regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular HS endosulfatase Sulf1 results in increased ISC division during normal homeostasis, which is 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 HS structural modifications provides a novel regulatory step for precise temporal control of stem cell activity during regeneration.组织损伤可激活干细胞分裂以启动再生。目前对于再生结束阶段如何对干细胞有丝分裂活性进行适度抑制的分子机制，学界仍知之甚少。 本研究证实，乙酰肝素硫酸盐（heparan sulfate, HS）的特定修饰，在调控果蝇肠道干细胞（Drosophila intestinal stem cell, ISC）的正常中肠稳态及再生过程中的分裂活动中发挥关键作用。细胞外HS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，该现象由JAK/STAT、表皮生长因子受体（EGFR）及Hedgehog等促有丝分裂信号通路的上调所介导。 通过再生模型实验，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，这表明Sulf1是再生结束时终止ISC分裂的必需因子。 我们据此提出，通过HS的结构修饰对促分裂原信号进行转录后调控，可为再生过程中干细胞活性的精准时间调控提供一种全新的调控途径。