Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Cell Stem Cell. 2017 Dec 7;21(6):730-746.e6. doi: 10.1016/j.stem.2017.10.011. Epub 2017 Nov 9.
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.
器官发生产生包含功能亚基、连接成分和祖细胞龛的高级结构。尽管基于类器官的组织发育建模最近取得了进展，但从多能干细胞 (PSC) 中重现这些复杂结构仍然具有挑战性。在这项研究中，我们报告了肾类器官的组装，这些类器官再现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，我们建立了从鼠和人 PSC 中差异诱导每个谱系的方案，输尿管芽包含经历分支形态发生的上皮肾祖细胞，从而在协调器官几何形状方面发挥核心作用，以及相邻的间质肾祖细胞。重要的是，重新组装的类器官发育出了胚胎肾脏的固有结构，包括外围祖细胞龛和内部分化的肾单位，它们通过分支的输尿管上皮相互连接。这种选择性诱导和重新组装策略将是在 PSC 衍生的类器官中再现器官型结构的有力方法。
