Heparan sulfate maintains adult midgut homeostasis in Drosophila
Heparan sulfate maintains adult midgut homeostasis in Drosophila
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DOI：
10.1002/cbin.11289
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发表时间：
2019-12
影响因子：
3.9
通讯作者：
Min Wei;Lin Shi;Ruiyan Kong;Hang Zhao;Zhouhua Li
中科院分区：
文献类型：
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作者：
Min Wei;Lin Shi;Ruiyan Kong;Hang Zhao;Zhouhua Li
组织动态平衡由居住祖细胞(干细胞)的分化后代控制。成体干细胞不断调整其增殖/分化速率，以应对组织损伤和应激。然而，分化的细胞如何维持组织的动态平衡仍不清楚。在这里，我们发现硫酸乙酰肝素(HS)，一类糖胺聚糖链(GAG)，可以保护分化的细胞免于丢失，以维持肠道内环境的稳定。肠上皮细胞(ECs)中HS的耗竭会导致肠内稳态的破坏，导致肠干细胞(ISC)样细胞的聚集和错误分化的后代。HS缺陷的内皮细胞容易发生细胞死亡/应激，并诱导细胞因子和表皮生长因子(EGF)的表达，进而促进ISC的增殖和分化。有趣的是，内皮细胞中HS的耗竭导致去五指肠麻痹(DPP)信号失活。此外，异位DPP信号完全挽救了HS耗竭造成的缺陷。综上所述，我们的数据表明，HS是内皮细胞激活DPP信号所必需的，从而保护内皮细胞免受消融，以维持中肠内环境平衡。我们的数据揭示了分化细胞如何有助于维持组织动态平衡的调节机制。
Tissue homeostasis is controlled by the differentiated progeny of residential progenitors (stem cells). Adult stem cells constantly adjust their proliferation/differentiation rates to respond to tissue damage and stresses. However, how differentiated cells maintain tissue homeostasis remains unclear. Here, we find that heparan sulfate (HS), a class of glycosaminoglycan (GAG) chains, protects differentiated cells from loss to maintain intestinal homeostasis. HS depletion in enterocytes (ECs) leads to intestinal homeostasis disruption, with accumulation of intestinal stem cell (ISC)‐like cells and mis‐differentiated progeny. HS‐deficient ECs are prone to cell death/stress and induced cytokine and epidermal growth factor (EGF) expression, which, in turn, promote ISC proliferation and differentiation. Interestingly, HS depletion in ECs results in the inactivation of decapentaplegic (Dpp) signaling. Moreover, ectopic Dpp signaling completely rescued the defects caused by HS depletion. Together, our data demonstrate that HS is required for Dpp signal activation in ECs, thereby protecting ECs from ablation to maintain midgut homeostasis. Our data shed light into the regulatory mechanisms of how differentiated cells contribute to tissue homeostasis maintenance.