Nephron progenitor commitment is a stochastic process influenced by cell migration
- Murdoch Children's Research Institute, Australia
- University of Queensland, Australia
- Cincinnati Children's Hospital Medical Center, United States
- Murdoch Childrens Research Institute, Australia
- 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.
Article and author information
Author details
Alexander Nicholas Combes
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
- Elizabeth Robertson, University of Oxford, United Kingdom
Version history
- Received: August 16, 2018
- Accepted: January 23, 2019
- Accepted Manuscript published: January 24, 2019 (version 1)
- 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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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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