Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling
Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling
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DOI：
10.7554/elife.15034
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发表时间：
2016-07-19
期刊：
影响因子：
7.7
通讯作者：
Itoh, Tohru
中科院分区：
文献类型：
--
作者：
Kamimoto, Kenji;Kaneko, Kota;Itoh, Tohru
肝内胆管上皮组织的动态重塑在肝再生中起着关键作用，但这一过程的细胞基础仍不清楚。我们采取了一种无偏的方法，基于在体内克隆标记和跟踪的胆管上皮细胞的三维景观，结合数学模拟，以了解其增殖模式的小鼠肝损伤模型中，新生的胆管结构形成的组织内在的方式。观察到胆管上皮细胞之间存在明显的异质性：而大多数在损伤后进入细胞周期的应答者表现出有限的和逐渐减少的生长潜力，选择的群体继续增殖，在维持胆管扩张方面做出了重大贡献。我们的研究突出了上皮组织动力学的独特模式，其不依赖于固定干细胞驱动的分级系统，而是依赖于具有持续增殖活性的随机维持的祖细胞群体。
Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity.