Dissecting the Global Dynamic Molecular Profiles of Human Fetal Kidney Development by Single-Cell RNA Sequencing

Healthy renal function depends on normal nephrogenesis during embryonic development. However, a comprehensive gene expression profile of human fetal kidney development remains largely unexplored. Here, using a single-cell RNA-sequencing technique, we analyzed >3,000 human fetal renal cells spanning 4 months of development in utero. Unsupervised analysis identified two progenitor subtypes during cap mesenchyme development, suggesting a mechanism for sustaining their progenitor states. Furthermore, we identified critical transcriptional regulators and signaling pathways involved in the segmentation of nephron tubules. We explored the development of the highly heterogeneous collecting duct epithelia and dissected the metabolic gene repertoire and the extracellular matrix composition of the glomerular mesangium. The results provide insights on the molecular basis and regulatory events in human renal development. Moreover, the cell-type-specific expression features of causal genes in congenital renal diseases may be helpful in the treatment of these diseases. [Display omitted] •Nephron progenitor cell subpopulations and their signature genes are identified•NOTCH, PI3K, and WNT signaling pathways participate in nephron tubule segmentation•Extracellular matrix composition defines the maturation of glomerular mesangium•Congenital renal disease risk genes expressed in specific cell types in fetal kidney To investigate the gene expression profiles of human fetal kidney development, Wang et al. performed single-cell RNA-seq for >3,000 renal cells. They highlight the heterogeneity of cap mesenchyme and regulatory factors in nephron formation. The results reveal cell-type-specific risk genes in congenital renal diseases.