Organoid vs In Vivo Mouse Model: Which is Better Research Tool to Understand the Biologic Mechanisms of Intestinal Epithelium?
Organoid vs In Vivo Mouse Model: Which is Better Research Tool to Understand the Biologic Mechanisms of Intestinal Epithelium?
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DOI：
10.1016/j.jcmgh.2021.06.027
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发表时间：
2022
影响因子：
7.2
通讯作者：
Sato T
中科院分区：
文献类型：
--
作者：
Sugimoto S;Sato T
哺乳动物肠上皮由腺组织学单位、隐窝组成。地穴具有显着的自我更新能力，整个单位在几天内不断再生。自我更新能力有助于体内平衡，并且在肠道损伤后至关重要，此时必须从裸露的粘膜形成新的隐窝。小鼠模型让人们了解隐窝如何再生以及哪些因素调节隐窝的自我更新。 20 世纪 70 年代，Leblond、Cheng 和 Bjerknes 揭示了小鼠肠隐窝的自我更新动态，并提出负责隐窝自我更新的肠干细胞 (ISC)。 1, 2 然而，直到使用小鼠遗传模型的谱系追踪系统出现后，ISC 才被正式鉴定，此时 Barker 和 Clevers 证明了 Lgr5+ ISC 的长期自我更新潜力和多分化能力。 3 Lgr5 表达表明 Wnt 信号传导在 ISC 维持中的关键作用。此外，这一发现强调了微环境因素（称为生态位因素）可用于支持 ISC。 Sato 和 Clevers 结合使用 EGF（生长因子）、Noggin（Bmp 抑制剂）和 R-spondin（Wnt 信号激活剂）等利基因子，开发了一种用于小鼠小肠上皮的类器官培养系统。 4 自从类器官培养系统建立以来，小鼠遗传模型和类器官一直是研究 ISC 和隐窝发育的两种主要工具。在这里，我们讨论类器官培养系统相对于小鼠遗传模型的优势（表 1）。
The mammalian intestinal epithelium consists of the glandular histologic unit, crypts. Crypts have a remarkable self-renewing capacity, and the entire unit is constantly regenerated within several days. The self-renewing capacity is instrumental for homeostasis and critical after intestinal injury, when new crypts must be formed from a landscape of denuded mucosa. Mouse models have provided an understanding of how crypts regenerate and which factors regulate the self-renewal of crypts. In the 1970s, Leblond, Cheng, and Bjerknes revealed the self-renewing dynamics of mouse intestinal crypts and proposed intestinal stem cells (ISCs) responsible for crypt self-renewal. 1, 2 However, ISCs were not formally identified until the emergence of a lineage tracing system using mouse genetic models, when Barker and Clevers demonstrated the long-term self-renewing potential and multidifferentiation capacity of Lgr5+ ISCs. 3 The Lgr5 expression indicated the critical role of Wnt signaling in the maintenance of ISCs. Moreover, this finding underscored that microenvironmental factors, referred to as niche factors, could be used to support ISCs. Using a combination of niche factors including EGF (growth factor), Noggin (Bmp inhibitor), and R-spondin (Wnt signaling activator), Sato and Clevers developed an organoid culture system for mouse small intestinal epithelium. 4 Ever since the establishment of the organoid culture system, mouse genetic models and organoids have been 2 major tools to study ISCs and crypt development. Here, we discuss the advantages of the organoid culture system over mouse genetic models (Table 1).
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影响因子：
9.8
作者：
Langlands, Alistair J.;Almet, Axel A.;Nathke, Inke S.
通讯作者：
Nathke, Inke S.
影响因子：
29.4
作者：
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影响因子：
64.8
作者：
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通讯作者：
Clevers, Hans
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64.8
作者：
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通讯作者：
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