The mammalian kidney develops through reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons. Most of our knowledge of the developmental regulators driving this process arises from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories during development. Single-cell transcriptome analyses of 6414 cells from five individual specimens identified 11 initial clusters of specific renal cell types as defined by their gene expression profile. Further subclustering identifies progenitors, and mature and intermediate stages of differentiation for several renal lineages. Other lineages identified include mesangium, stroma, endothelial and immune cells. Novel markers for these cell types were revealed in the analysis, as were components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression profile of the developing human kidney at the single-cell level.
Bibliographical noteFunding Information:
This work is funded by a National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases ReBuilding a Kidney (RBK) Consortium Partnership Project to J.R.S. (U01 DK107350). The University of Washington Laboratory of Developmental Biology was supported by a Eunice Kennedy Shriver National Institute of Child Health and Human Development award (5R24HD000836). Support was also provided from the University of Michigan Center for Gastrointestinal Research (UMCGR), funded by the National Institute of Diabetes and Digestive and Kidney Diseases (5P30DK034933). Deposited in PMC for immediate release.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Developmental Biology