Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based modeling of tissue development, recapitulating these complex configurations from pluripotent stem cells (PSCs) has remained challenging. In this study, we report assembly of kidney organoids that recapitulate embryonic branching morphogenesis. By studying the distinct origins and developmental processes of the ureteric bud, which contains epithelial kidney progenitors that undergo branching morphogenesis and thereby plays a central role in orchestrating organ geometry, and neighboring mesenchymal nephron progenitors, we established a protocol for differential induction of each lineage from mouse and human PSCs. Importantly, reassembled organoids developed the inherent architectures of the embryonic kidney, including the peripheral progenitor niche and internally differentiated nephrons that were interconnected by a ramified ureteric epithelium. This selective induction and reassembly strategy will be a powerful approach to recapitulate organotypic architecture in PSC-derived organoids.

中文翻译：

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来自多能干细胞的高阶肾脏器官发生。

器官发生产生包含功能性亚基，结缔成分和祖先壁ches的高级结构。尽管最近在基于类器官的组织发展模型方面取得了进展，但从多能干细胞（PSC）概括这些复杂的构型仍然具有挑战性。在这项研究中，我们报告了肾脏类器官的组装，概括了胚胎分支形态发生。通过研究输尿管芽的不同起源和发育过程，输尿管芽包含上皮肾脏祖细胞，它们经历分支形态发生，从而在协调器官的几何结构以及邻近的间充质肾祖细胞中起着核心作用，我们建立了一种协议，用于从中分化出每个谱系小鼠和人类PSC。重要的，重新组装的类器官形成了胚胎肾脏的固有结构，包括周围的祖细胞生态位和内部分化的肾单位，这些肾单位通过分枝的输尿管上皮相互连接。这种选择性的诱导和重组策略将是概述源自PSC的类器官中器官型结构的有力方法。