Lgr5+ Stem Cells Are Indispensable for Radiation-Induced Intestinal Regeneration
Lgr5+ Stem Cells Are Indispensable for Radiation-Induced Intestinal Regeneration
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DOI：
10.1016/j.stem.2013.11.008
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发表时间：
2014-02-06
期刊：
影响因子：
23.9
通讯作者：
de Sauvage, Frederic J.
中科院分区：
文献类型：
--
作者：
Metcalfe, Ciara;Kljavin, Noelyn M.;de Sauvage, Frederic J.
肠上皮不断自我更新，并能在损伤后迅速再生。Lgr 5标记有丝分裂活性的肠干细胞（ISCs）。重要的是，由于Lgr 5（-）储备ISCs的激活，在Lgr 5（+）细胞耗尽后可以维持肠内稳态。Lgr 5（-）ISC群体被认为在辐射诱导的损伤后的肠再生过程中发挥类似的作用。我们通过将Lgr 5（+）ISCs的耗竭与辐射暴露相结合来测试这种再生假设。与体内平衡期间Lgr 5（+）ISC损失的可忽略的影响相反，在辐射诱导的损伤和随后的修复期间Lgr 5（+）细胞的消耗引起灾难性的隐窝损失和隐窝-绒毛结构的恶化。有趣的是，我们发现缺乏Lgr 5（+）细胞的隐窝在Apc缺失时能够经历增生。这些数据表明，Lgr 5（+）储备干细胞对辐射敏感，Lgr 5（+）细胞对辐射暴露后的肠道再生至关重要，但对癌前过度增殖至关重要。
The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5(+) cells due to the activation of Lgr5(-) reserve ISCs. The Lgr5(-) ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5(+) ISCs with radiation exposure. In contrast to the negligible effect of Lgr5(+) ISC loss during homeostasis, depletion of Lgr5(+) cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5(+) cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5(+) reserve stem cells are radiosensitive and that Lgr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.