Journal article

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

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2019

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 an..

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Grants

Awarded by National Health and Medical Research Council


Awarded by Australian Research Council


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

National Health and Medical Research Council GNT1156567 Alexander N CombesAustralian Research Council DE150100652 Alexander N CombesMurdoch Children's Research Institute Alexander N CombesNational Health and Medical Research Council GNT1136085 Melissa H LittleNational Health and Medical Research Council GNT1063989 Melissa H LittleThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.