Thyroid hormone-induced cell-cell interactions are required for the development of adult intestinal stem cells.
Thyroid hormone-induced cell-cell interactions are required for the development of adult intestinal stem cells.
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DOI：
10.1186/2045-3701-3-18
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发表时间：
2013-04-01
影响因子：
7.5
通讯作者：
Ishizuya-Oka A
中科院分区：
文献类型：
--
作者：
Hasebe T;Fu L;Miller TC;Zhang Y;Shi YB;Ishizuya-Oka A
长期以来，哺乳动物肠道一直被用作研究器官特异性成体干细胞的模型，这些干细胞对整个成年期的器官修复和组织再生至关重要。肠上皮细胞自我更新系统的建立发生在围产期发育过程中，绒毛-隐窝轴的建立与隐窝内成体干细胞的定位。这一发育时期的特点是血浆甲状腺激素（T3）水平高，已知T3缺乏会损害肠道发育。由于母体的影响，确定T3如何调节哺乳动物肠道中成体干细胞的发育可能很困难。两栖动物蜕变过程中的肠道重塑类似于哺乳动物围产期肠道成熟，其对T3的依赖性已得到充分证实。两栖动物模型的一个主要优点是，它可以很容易地通过改变T3的可用性来控制。操纵和检查成体干细胞相对快速和局部形成的能力极大地帮助阐明了调节其形成的分子机制，并进一步揭示了支持脊椎动物成体干细胞发育潜在机制保护的证据。此外，对非洲爪蟾的遗传研究表明，T3在上皮和肠道其余部分（很可能是潜在结缔组织）中的作用是成体干细胞形成所必需的。分子分析表明，涉及刺猬蛋白和BMP通路的细胞间相互作用对于干细胞生态位的建立至关重要，而干细胞生态位对于成体肠道干细胞的形成至关重要。
The mammalian intestine has long been used as a model to study organ-specific adult stem cells, which are essential for organ repair and tissue regeneration throughout adult life. The establishment of the intestinal epithelial cell self-renewing system takes place during perinatal development when the villus-crypt axis is established with the adult stem cells localized in the crypt. This developmental period is characterized by high levels of plasma thyroid hormone (T3) and T3 deficiency is known to impair intestinal development. Determining how T3 regulates adult stem cell development in the mammalian intestine can be difficult due to maternal influences. Intestinal remodeling during amphibian metamorphosis resembles perinatal intestinal maturation in mammals and its dependence on T3 is well established. A major advantage of the amphibian model is that it can easily be controlled by altering the availability of T3. The ability to manipulate and examine this relatively rapid and localized formation of adult stem cells has greatly assisted in the elucidation of molecular mechanisms regulating their formation and further revealed evidence that supports conservation in the underlying mechanisms of adult stem cell development in vertebrates. Furthermore, genetic studies in Xenopus laevis indicate that T3 actions in both the epithelium and the rest of the intestine, most likely the underlying connective tissue, are required for the formation of adult stem cells. Molecular analyses suggest that cell-cell interactions involving hedgehog and BMP pathways are critical for the establishment of the stem cell niche that is essential for the formation of the adult intestinal stem cells.
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