Single-cell transcriptomics reveals gene expression dynamics of human fetal kidney development

PLoS Biol. 2019 Feb 21;17(2):e3000152. doi: 10.1371/journal.pbio.3000152. eCollection 2019 Feb.

Abstract

The current understanding of mammalian kidney development is largely based on mouse models. Recent landmark studies revealed pervasive differences in renal embryogenesis between mouse and human. The scarcity of detailed gene expression data in humans therefore hampers a thorough understanding of human kidney development and the possible developmental origin of kidney diseases. In this paper, we present a single-cell transcriptomics study of the human fetal kidney. We identified 22 cell types and a host of marker genes. Comparison of samples from different developmental ages revealed continuous gene expression changes in podocytes. To demonstrate the usefulness of our data set, we explored the heterogeneity of the nephrogenic niche, localized podocyte precursors, and confirmed disease-associated marker genes. With close to 18,000 renal cells from five different developmental ages, this study provides a rich resource for the elucidation of human kidney development, easily accessible through an interactive web application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Lineage / genetics
  • Datasets as Topic
  • Female
  • Fetal Development
  • Fetus
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Ontology
  • Gestational Age
  • Humans
  • Kidney / cytology
  • Kidney / growth & development
  • Kidney / metabolism*
  • Male
  • Molecular Sequence Annotation
  • Organogenesis / genetics*
  • Podocytes / cytology
  • Podocytes / metabolism*
  • Single-Cell Analysis
  • Transcriptome*

Grant support

M. H., P. v.d. B., N. B.-C. and S.S. were supported by the Netherlands Organisation for Scientific Research (NWO/OCW, www.nwo.nl), as part of the Frontiers of Nanoscience (NanoFront) program. E.A. acknowledges support by a Stichting voor Fundamenteel Onderzoek der Materie (FOM, www.nwo.nl) projectruimte grant (16PR1040). X.F. was supported by the China Scholarship Council (www.cscscholarships.net, 201307040026). M.B. and S.M.C.S.L. were supported by an European Research council Consolidator Grant (https://erc.europa.eu/, ERC-CoG-2016-725722). We further acknowledge support from Generade (https://www.hsleiden.nl/generade, project number G2016-14). This work was carried out on the Dutch national e-infrastructure with the support of SURF Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.