Nephron progenitor commitment is a stochastic process influenced by cell migration

Kynan T. Lawlor, Luke Zappia, James Lefevre, Joo Seop Park, Nicholas A. Hamilton, Alicia Oshlack, Melissa H. Little, Alexander N. Combes

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Article numbere41156
Number of pages24
JournaleLife
Volume8
DOIs
Publication statusPublished - 24 Jan 2019
Externally publishedYes

Keywords

  • cell migration
  • developmental biology
  • kidney development
  • mouse
  • nephron progenitor
  • regenerative medicine
  • single cell transcriptional profiling
  • stem cells
  • stochastic induction
  • Wnt4

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