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

SummaryAdult 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) comprise a unique, unipotent regenerative compartment. RSCs respond only to loss of nearby principal cells (PCs), cells critical for maintaining ionic balance. Perhaps due to the large size of PCs they are outnumbered by RSCs, which replace each lost cell with multiple PCs of lower ploidy. RSCs share a developmental origin with highly active intestinal stem cells (ISCs), and like ISCs generate daughters by asymmetric Notch signaling, yet RSCs remain quiescent in the absence of 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.

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

eLife ◽

10.7554/elife.54096 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Chenhui Wang ◽

Allan C Spradling

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Kidney Stones ◽

Stellate Cells ◽

Malpighian Tubules ◽

Stem Cell Population ◽

Ionic Balance ◽

Cell Turnover ◽

Principal Cells ◽

Adult Drosophila

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 Drosophilarenal 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.

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Faculty Opinions recommendation of Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1162228.622703 ◽

2009 ◽

Author(s):

Ralf Paus ◽

Jennifer Elisabeth Klöpper

Keyword(s):

Stem Cell ◽

Cell Population ◽

Stem Cell Population ◽

Multipotent Stem Cell

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Faculty Opinions recommendation of Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718277923.793527548 ◽

2017 ◽

Author(s):

Pura Muñoz-Cánoves

Keyword(s):

Stem Cell ◽

Cell Population ◽

Stem Cell Population ◽

Muscle Stem Cell

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Faculty Opinions recommendation of Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718277923.793492340 ◽

2014 ◽

Author(s):

Angel Nebreda ◽

Marçal Vilar

Keyword(s):

Stem Cell ◽

Cell Population ◽

Stem Cell Population ◽

Muscle Stem Cell

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Targeting DNA Methylation Depletes Uterine Leiomyoma Stem Cell–enriched Population by Stimulating Their Differentiation

Endocrinology ◽

10.1210/endocr/bqaa143 ◽

2020 ◽

Vol 161 (10) ◽

Cited By ~ 2

Author(s):

Shimeng Liu ◽

Ping Yin ◽

Jingting Xu ◽

Ariel J Dotts ◽

Stacy A Kujawa ◽

...

Keyword(s):

Dna Methylation ◽

Stem Cell ◽

Cell Population ◽

Uterine Leiomyoma ◽

Stem Cell Population ◽

Epigenetic Landscape ◽

Stem Cell Regulation ◽

Integrative Analyses ◽

Associated Functions ◽

Intermediate Cells

Abstract Uterine leiomyoma (LM) is the most common tumor in women and can cause severe morbidity. Leiomyoma growth requires the maintenance and proliferation of a stem cell population. Dysregulated deoxyribonucleic acid (DNA) methylation has been reported in LM, but its role in LM stem cell regulation remains unclear. Here, we fluorescence-activated cell sorting (FACS)-sorted cells from human LM tissues into 3 populations: LM stem cell–like cells (LSC, 5%), LM intermediate cells (LIC, 7%), and differentiated LM cells (LDC, 88%), and we analyzed the transcriptome and epigenetic landscape of LM cells at different differentiation stages. Leiomyoma stem cell–like cells harbored a unique methylome, with 8862 differentially methylated regions compared to LIC and 9444 compared to LDC, most of which were hypermethylated. Consistent with global hypermethylation, transcript levels of TET1 and TET3 methylcytosine dioxygenases were lower in LSC. Integrative analyses revealed an inverse relationship between methylation and gene expression changes during LSC differentiation. In LSC, hypermethylation suppressed the genes important for myometrium- and LM-associated functions, including muscle contraction and hormone action, to maintain stemness. The hypomethylating drug, 5′-Aza, stimulated LSC differentiation, depleting the stem cell population and inhibiting tumor initiation. Our data suggest that DNA methylation maintains the pool of LSC, which is critical for the regeneration of LM tumors.

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