Ide Hiroshi, Miike Koichiro, Ohmori Tomoko, Maruyama Kosuke, Izumi Yuichiro, Tanigawa Shunsuke, Nishinakamura Ryuichi
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Sci Rep. 2024 Dec 5;14(1):30293. doi: 10.1038/s41598-024-81984-w.
Kidney organoids are connected to the host circulation and mature after transplantation. However, they are still immature compared to the adult kidneys, and their precise maturation stages remain unclear. By transplanting the mouse embryonic kidney as a model system for organoid transplantation, we report here the maturation defects of the graft, especially in the medulla. Single cell profiling of the developing kidneys in vivo identified gene sets associated with the maturation of the collecting duct epithelium and medullary stroma. These data revealed an upregulation of genes associated with channel/transporter functions and immune defense, as well as a downregulation of neuronal genes. Using these marker genes, we found that the maturation of the collecting duct and medullary stroma in the grafts barely corresponds to the perinatal stage, which was confirmed histologically by using representative genes. Thus, the gene sets obtained serve as maturation coordinates for the renal medulla and will be helpful in analyzing its maturation defects after transplantation. They will also provide a useful basis for further maturation of transplanted kidney organoids.
肾类器官与宿主循环系统相连，并在移植后成熟。然而，与成年肾脏相比，它们仍然不成熟，其精确的成熟阶段仍不清楚。通过移植小鼠胚胎肾脏作为类器官移植的模型系统，我们在此报告了移植物的成熟缺陷，尤其是在髓质。对体内发育中的肾脏进行单细胞分析，确定了与集合管上皮和髓质基质成熟相关的基因集。这些数据显示与通道/转运蛋白功能和免疫防御相关的基因上调，以及神经元基因下调。利用这些标记基因，我们发现移植物中集合管和髓质基质的成熟几乎与围产期阶段相对应，这通过使用代表性基因进行组织学证实。因此，获得的基因集可作为肾髓质的成熟坐标，有助于分析其移植后的成熟缺陷。它们还将为移植的肾类器官的进一步成熟提供有用的基础。
