Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch.
Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch.
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DOI：
10.15252/embj.201591517
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发表时间：
2015-08-04
期刊：
影响因子：
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通讯作者：
Dominguez M
中科院分区：
文献类型：
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作者：
Antonello ZA;Reiff T;Ballesta-Illan E;Dominguez M
尽管有扰动和需求的不确定性，肠上皮仍然非常强健。在这里，我们使用新颖的追踪方法来研究这种鲁棒性的基础，该方法可以同时捕获干细胞和固定祖细胞（称为成肠细胞）的动态以及具有时空分辨率的肠细胞周转。我们发现肠道干细胞（ISCs）在果蝇中肠稳态过程中“提前”分裂。另一方面，它们的新生肠母细胞呈现高度极化的形状，具有侵袭性和运动性。它们延伸出长长的膜突起，使细胞与成熟细胞接触，同时行使一种延迟细胞最终分化的能力，直到局部需求实现。这种细胞可塑性与蜗牛家族基因蜗牛介导的上皮-间质转化（EMT）程序有机制联系。在“暂停”的肠母细胞中激活保守的microRNA miR-8/miR-200，以响应局部细胞损失，通过拮抗蜗牛，通过反向MET促进及时的终末分化。我们的研究结果揭示了强大的肠道更新依赖于迄今为止尚未认识到的肠母细胞的可塑性，并揭示了它们在感知和/或响应当地需求方面的积极作用。
The intestinal epithelium is remarkably robust despite perturbations and demand uncertainty. Here, we investigate the basis of such robustness using novel tracing methods that allow simultaneously capturing the dynamics of stem and committed progenitor cells (called enteroblasts) and intestinal cell turnover with spatiotemporal resolution. We found that intestinal stem cells (ISCs) divide “ahead” of demand during Drosophila midgut homeostasis. Their newborn enteroblasts, on the other hand, take on a highly polarized shape, acquire invasive properties and motility. They extend long membrane protrusions that make cell–cell contact with mature cells, while exercising a capacity to delay their final differentiation until a local demand materializes. This cellular plasticity is mechanistically linked to the epithelial–mesenchymal transition (EMT) programme mediated by escargot, a snail family gene. Activation of the conserved microRNA miR-8/miR-200 in “pausing” enteroblasts in response to a local cell loss promotes timely terminal differentiation via a reverse MET by antagonizing escargot. Our findings unveil that robust intestinal renewal relies on hitherto unrecognized plasticity in enteroblasts and reveal their active role in sensing and/or responding to local demand.