Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA–protein kinase catalytic subunit (prkdc), interleukin-2 receptor γ a (il2rga), and double-homozygous–mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish.

单细胞转录组谱分析的最新进展为研究组织和器官发育过程中的细胞异质性提供了前所未有的途径。在这项研究中，我们使用大规模平行的单细胞RNA测序来定义斑马鱼肾脏内的细胞异质性，构建了在成年斑马鱼中发现的确定性造血和功能独特的肾细胞的综合分子图谱。因为我们的方法以无偏方式分析血液和肾脏细胞，我们的方法是DNA-蛋白内表征免疫细胞缺陷有用激酶催化亚单位（PRKDC），白细胞介素-2受体γ一个（il2rga）和双纯合突变鱼类，确定特定遗传突变体中T，B和自然杀伤细胞的血细胞损失。我们的分析还发现了新型细胞类型，包括两类天然杀伤性免疫细胞，即经典定义的和类红血球引发的造血干细胞和祖细胞，分泌粘蛋白的肾细胞以及肾干/祖细胞。总的来说，我们的工作为成年斑马鱼的肾脏和骨髓细胞提供了首个全面的单细胞转录组学分析。