Nephron progenitor commitment is a stochastic process influenced by cell migration

Elife. 2019 Jan 24:8:e41156. doi: 10.7554/eLife.41156.

Abstract

Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express Wnt4, an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction. This plasticity may enable robust regulation of nephrogenesis as niches remodel and grow during organogenesis.

Keywords: Wnt4; cell migration; developmental biology; kidney development; mouse; nephron progenitor; regenerative medicine; single cell transcriptional profiling; stem cells; stochastic induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage*
  • Cell Movement*
  • Computer Simulation
  • Female
  • Mice, Inbred C57BL
  • Models, Biological
  • Nephrons / cytology*
  • Stem Cell Niche
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Stochastic Processes
  • Transcription, Genetic
  • Wnt4 Protein / metabolism

Substances

  • Wnt4 Protein