Nephron progenitor commitment is a stochastic process influenced by cell migration

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...

Full description

Bibliographic Details
Main Authors: Kynan T Lawlor, Luke Zappia, James Lefevre, Joo-Seop Park, Nicholas A Hamilton, Alicia Oshlack, Melissa H Little, Alexander N Combes
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/41156
_version_ 1811253171081707520
author Kynan T Lawlor
Luke Zappia
James Lefevre
Joo-Seop Park
Nicholas A Hamilton
Alicia Oshlack
Melissa H Little
Alexander N Combes
author_facet Kynan T Lawlor
Luke Zappia
James Lefevre
Joo-Seop Park
Nicholas A Hamilton
Alicia Oshlack
Melissa H Little
Alexander N Combes
author_sort Kynan T Lawlor
collection DOAJ
description 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.
first_indexed 2024-04-12T16:46:52Z
format Article
id doaj.art-346dcaa82adf4a93883b05f34c9ad703
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-04-12T16:46:52Z
publishDate 2019-01-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-346dcaa82adf4a93883b05f34c9ad7032022-12-22T03:24:33ZengeLife Sciences Publications LtdeLife2050-084X2019-01-01810.7554/eLife.41156Nephron progenitor commitment is a stochastic process influenced by cell migrationKynan T Lawlor0https://orcid.org/0000-0003-4080-5439Luke Zappia1https://orcid.org/0000-0001-7744-8565James Lefevre2Joo-Seop Park3Nicholas A Hamilton4https://orcid.org/0000-0003-0331-3427Alicia Oshlack5https://orcid.org/0000-0001-9788-5690Melissa H Little6Alexander N Combes7https://orcid.org/0000-0001-6008-8786Murdoch Children's Research Institute, Parkville, AustraliaMurdoch Children's Research Institute, Parkville, Australia; School of Biosciences, University of Melbourne, Melbourne, AustraliaDivision of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AustraliaDivision of Pediatric Urology and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, United StatesDivision of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, AustraliaMurdoch Children's Research Institute, Parkville, Australia; School of Biosciences, University of Melbourne, Melbourne, AustraliaMurdoch Children's Research Institute, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, AustraliaMurdoch Children's Research Institute, Parkville, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, AustraliaProgenitor 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.https://elifesciences.org/articles/41156kidney developmentnephron progenitorcell migrationsingle cell transcriptional profilingWnt4stochastic induction
spellingShingle Kynan T Lawlor
Luke Zappia
James Lefevre
Joo-Seop Park
Nicholas A Hamilton
Alicia Oshlack
Melissa H Little
Alexander N Combes
Nephron progenitor commitment is a stochastic process influenced by cell migration
eLife
kidney development
nephron progenitor
cell migration
single cell transcriptional profiling
Wnt4
stochastic induction
title Nephron progenitor commitment is a stochastic process influenced by cell migration
title_full Nephron progenitor commitment is a stochastic process influenced by cell migration
title_fullStr Nephron progenitor commitment is a stochastic process influenced by cell migration
title_full_unstemmed Nephron progenitor commitment is a stochastic process influenced by cell migration
title_short Nephron progenitor commitment is a stochastic process influenced by cell migration
title_sort nephron progenitor commitment is a stochastic process influenced by cell migration
topic kidney development
nephron progenitor
cell migration
single cell transcriptional profiling
Wnt4
stochastic induction
url https://elifesciences.org/articles/41156
work_keys_str_mv AT kynantlawlor nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT lukezappia nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT jameslefevre nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT jooseoppark nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT nicholasahamilton nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT aliciaoshlack nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT melissahlittle nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration
AT alexanderncombes nephronprogenitorcommitmentisastochasticprocessinfluencedbycellmigration