Recent advances in stem cell biology have enabled the generation of kidney organoids in vitro, and further maturation of these organoids is observed after experimental transplantation. However, the current organoids remain immature and their precise maturation stages are difficult to determine because of limited information on developmental stage-dependent gene expressions in the kidney in vivo. To establish relevant molecular coordinates, we performed single-cell RNA sequencing (scRNA-seq) on developing kidneys at different stages in the mouse. By selecting genes that exhibited upregulation at birth compared with embryonic day 15.5 as well as cell lineage-specific expression, we generated gene lists correlated with developmental stages in individual cell lineages. Application of these lists to transplanted embryonic kidneys revealed that most cell types, other than the collecting ducts, exhibited similar maturation to kidneys at the neonatal stage in vivo, revealing non-synchronous maturation across the cell lineages. Thus, our scRNA-seq data can serve as useful molecular coordinates to assess the maturation of developing kidneys and eventually of kidney organoids.

干细胞生物学的最新进展使得能够在体外产生肾脏类器官，并且在实验移植后观察到这些类器官的进一步成熟。但是，由于体内关于肾脏发育阶段相关基因表达的信息有限，目前的类器官仍然不成熟，并且难以确定其确切的成熟阶段。为了建立相关的分子坐标，我们在小鼠不同阶段的发育中的肾脏上进行了单细胞RNA测序（scRNA-seq）。通过选择与胚胎第15.5天相比在出生时表现出上调的基因以及细胞谱系特异性表达，我们生成了与单个细胞谱系的发育阶段相关的基因列表。将这些列表应用于已移植的​​胚胎肾脏后，发现除收集导管外，大多数细胞类型在体内新生儿阶段均表现出与肾脏相似的成熟度，从而揭示了整个细胞谱系的非同步成熟度。因此，我们的scRNA-seq数据可作为有用的分子坐标，用于评估发育中的肾脏以及最终肾脏类器官的成熟度。