Nephron progenitor commitment is a stochastic process influenced by cell migration

  1. Kynan T Lawlor
  2. Luke Zappia
  3. James Lefevre
  4. Joo-Seop Park
  5. Nicholas A Hamilton
  6. Alicia Oshlack
  7. Melissa H Little  Is a corresponding author
  8. Alexander Nicholas Combes  Is a corresponding author
  1. Murdoch Children's Research Institute, Australia
  2. University of Queensland, Australia
  3. Cincinnati Children's Hospital Medical Center, United States
  4. Murdoch Childrens Research Institute, Australia
  5. University of Melbourne, Australia

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.

Data availability

Single cell sequencing data has been deposited in GEO under accession code GSE118486. Gene lists from the single cell analysis and code for the simulation of cell migration and stochastic commitment have been provided as Supplementary Files.

The following data sets were generated

Article and author information

Author details

  1. Kynan T Lawlor

    Cell Biology, Murdoch Children's Research Institute, Parkville, Australia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4080-5439
  2. Luke Zappia

    Cell Biology, Murdoch Children's Research Institute, Parkville, Australia
    Competing interests
    No competing interests declared.
  3. James Lefevre

    Division of Genomics of Development and Disease, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
    Competing interests
    No competing interests declared.
  4. Joo-Seop Park

    Division of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    No competing interests declared.
  5. Nicholas A Hamilton

    Division of Genomics of Development and Disease, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
    Competing interests
    No competing interests declared.
  6. Alicia Oshlack

    Cell Biology, Murdoch Children's Research Institute, Parkville, Australia
    Competing interests
    No competing interests declared.
  7. Melissa H Little

    Kidney Development, Disease and Regeneration, Murdoch Childrens Research Institute, Parkville, Australia
    For correspondence
    Melissa.Little@mcri.edu.au
    Competing interests
    Melissa H Little, Has consulted for and received research funding from Organovo Inc.
  8. Alexander Nicholas Combes

    Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia
    For correspondence
    alexander.combes@unimelb.edu.au
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6008-8786

Funding

National Health and Medical Research Council (GNT1156567)

  • Alexander Nicholas Combes

Australian Research Council (DE150100652)

  • Alexander Nicholas Combes

Murdoch Children's Research Institute

  • Alexander Nicholas Combes

National Health and Medical Research Council (GNT1136085)

  • Melissa H Little

National Health and Medical Research Council (GNT1063989)

  • Melissa H Little

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were assessed and approved by the Murdoch Children's Research Institute Animal Ethics Committee (A783/A894) and were conducted in accordance with applicable Australian laws governing the care and use of animals for scientific purposes.

Reviewing Editor

  1. Elizabeth Robertson, University of Oxford, United Kingdom

Publication history

  1. Received: August 16, 2018
  2. Accepted: January 23, 2019
  3. Accepted Manuscript published: January 24, 2019 (version 1)
  4. Version of Record published: February 5, 2019 (version 2)

Copyright

© 2019, Lawlor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kynan T Lawlor
  2. Luke Zappia
  3. James Lefevre
  4. Joo-Seop Park
  5. Nicholas A Hamilton
  6. Alicia Oshlack
  7. Melissa H Little
  8. Alexander Nicholas Combes
(2019)
Nephron progenitor commitment is a stochastic process influenced by cell migration
eLife 8:e41156.
https://doi.org/10.7554/eLife.41156

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