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Dev Cell. 2015 Oct 12;35(1):49-62. doi: 10.1016/j.devcel.2015.09.009.

Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

Author information

1
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45220, USA.
2
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45220, USA.
3
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
4
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45220, USA. Electronic address: raphael.kopan@cchmc.org.

Abstract

During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis.

KEYWORDS:

Fgf20; aging; kidney; mTor; nephron; stem cells

PMID:
26460946
PMCID:
PMC4615609
DOI:
10.1016/j.devcel.2015.09.009
[Indexed for MEDLINE]
Free PMC Article

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