TitleSingle-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney.
Publication TypeJournal Article
Year of Publication2018
AuthorsMenon, R, Otto, EA, Kokoruda, A, Zhou, J, Zhang, Z, Yoon, E, Chen, Y-C, Troyanskaya, O, Spence, JR, Kretzler, M, Cebrián, C
JournalDevelopment
Volume145
Issue16
Date Published2018 08 30
ISSN1477-9129
KeywordsAnimals, Cell Lineage, Fetus, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Kidney, Mice, Signal Transduction, Stem Cells
Abstract

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.

DOI10.1242/dev.164038
Alternate JournalDevelopment
PubMed ID30166318
PubMed Central IDPMC6124540
Grant ListP30 DK034933 / DK / NIDDK NIH HHS / United States
R24 HD000836 / HD / NICHD NIH HHS / United States
U01 DK107350 / DK / NIDDK NIH HHS / United States