Hypothalamic-pituitary organoid generation through the recapitulation of organogenesis
Hypothalamic-pituitary organoid generation through the recapitulation of organogenesis
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通过器官发生的重演产生下丘脑-垂体类器官
DOI：
10.1111/dgd.12719
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Hiroshi Arima
中科院分区：
文献类型：
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作者：
Hajime Ozaki;Hidetaka Suga;Hiroshi Arima
本文综述了胚胎干细胞和诱导多能干细胞向下丘脑和垂体的发育和分化。重要的是在体内复制发育过程，以从ES/iPS细胞产生特定的细胞/类器官。我们还介绍了最新的研究结果，并讨论了未来的临床应用问题。神经外胚层祖细胞是通过在分化早期严格去除外源性图案化因子而从多能干细胞诱导而来的。诱导的祖细胞分化为吻侧下丘脑神经元，特别是大细胞加压素+神经元。在三维培养中，ES/iPS细胞分化为下丘脑神经外胚层和邻近的非神经头外胚层。Rathke囊状结构在两层之间的界面处自我组织，并产生各种内分泌细胞，包括促肾上腺皮质激素细胞和促生长激素细胞。我们的下一个目标是验证我们的逐步方法，以建立一种新的垂体功能减退症的移植治疗方法，并将其应用于发育性疾病模型。
This paper overviews the development and differentiation of the hypothalamus and pituitary gland from embryonic stem (ES) and induced pluripotent stem (iPS) cells. It is important to replicate the developmental process in vivo to create specific cells/organoids from ES/iPS cells. We also introduce the latest findings and discuss future issues for clinical application. Neuroectodermal progenitors are induced from pluripotent stem cells by strictly removing exogenous patterning factors during the early differentiation period. The induced progenitors differentiate into rostral hypothalamic neurons, in particular magnocellular vasopressin+neurons. In three‐dimensional cultures, ES/iPS cells differentiate into hypothalamic neuroectoderm and nonneural head ectoderm adjacently. Rathke’s pouch‐like structures self‐organize at the interface between the two layers and generate various endocrine cells, including corticotrophs and somatotrophs. Our next objective is to sophisticate our stepwise methodology to establish a novel transplantation treatment for hypopituitarism and apply it to developmental disease models.