Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis

Nils O. Lindström, Guilherme De Sena Brandine, Tracy Tran, Andrew Ransick, Gio Suh, Jinjin Guo, Albert D. Kim, Riana K. Parvez, Seth W. Ruffins, Elisabeth A. Rutledge, Matthew E. Thornton, Brendan Grubbs, Jill A. McMahon, Andrew D. Smith*, Andrew P. McMahon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. During kidney development, mammalian nephrons arise from a limited progenitor pool through a reiterative inductive process. Lindström et al. demonstrate that human and mouse nephron patterning involves gradual mesenchymal progenitor cell recruitment into the epithelial nephron precursor. Recruitment timing predicts precursor cell position and eventual fate in functional nephron structures.

Original languageEnglish (US)
Pages (from-to)651-660.e4
JournalDevelopmental Cell
Volume45
Issue number5
DOIs
StatePublished - Jun 4 2018

Keywords

  • fate
  • human
  • kidney
  • lineage
  • nephron
  • patterning
  • precursor
  • single-cell
  • time

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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