An abundant quiescent stem cell population in Drosophila Malpighian tubules protects principal cells from kidney stones

Abstract
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Abstract

Adult Drosophila Malpighian tubules have low rates of cell turnover but are vulnerable to damage caused by stones, like their mammalian counterparts, kidneys. We show that Drosophila renal stem cells (RSCs) in the ureter and lower tubules comprise a unique, unipotent regenerative compartment. RSCs respond only to loss of nearby principal cells (PCs), cells critical for maintaining ionic balance. Large polyploid PCs are outnumbered by RSCs, which replace each lost cell with multiple PCs of lower ploidy. Notably, RSCs do not replenish principal cells or stellate cells in the upper tubules. RSCs generate daughters by asymmetric Notch signaling, yet RSCs remain quiescent (cell cycle-arrested) without damage. Nevertheless, the capacity for RSC-mediated repair extends the lifespan of flies carrying kidney stones. We propose that abundant, RSC-like stem cells exist in other tissues with low rates of turnover where they may have been mistaken for differentiated tissue cells.

Data availability

Data submitted to NCBI under accession code PRJNA595625.

The following data sets were generated

1. Wang C
2. Spradling A
(2020) Transcriptional profiling of Drosophila ureter and lower tubules
NCBI Bioproject, PRJNA595625.

http://www.ncbi.nlm.nih.gov/bioproject/PRJNA595625

Article and author information

Author details

Chenhui Wang

Department of Embryology, Carnegie Institution for Science, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Allan C Spradling

Department of Embryology, Carnegie Institution for Science, Baltimore, United States

For correspondence
spradling@carnegiescience.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5251-1801

Funding

Howard Hughes Medical Institute (Allan Spradling)

Allan C Spradling

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

Copyright

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.