A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan

Jones, Brian Christopher; Wood, Jason G.; Chang, Chieh-Ming J.; Tam, Austin; Franklin, Michael J.; Siegel, Emily R.; Helfand, Stephen L.

doi:10.1038/ncomms13856

Cited by 98 publications

(108 citation statements)

References 41 publications

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“…Our study suggests that targeting Piwi and other chromatin remodeling pathways may be an effective way to delay or prevent age-associated loss of stem cell function. Interestingly, recent reports support the idea that Piwi expression and TE control in other somatic tissues influence organismal homeostasis and lifespan (Jones et al, 2016). Further studies comparing the relative effects of piwi loss of function on lifespan in a tissue-specific manner will contribute to our understanding of the different mechanisms through which the Piwi pathway contributes to tissue homeostasis.…”

Section: Discussionmentioning

confidence: 91%

“…The functions of Piwi outside the germline are only beginning to be explored (Ross et al, 2014). In differentiated somatic tissues, a physiologic function for the Piwi pathway has been reported in the brain and fat body of Drosophila (Janic et al, 2010; Jones et al, 2016). Piwi protein orthologues are also expressed in neoblasts of planaria (Reddien et al, 2005) and blastemal cells of salamander (Zhu et al, 2012), where they are required for efficient regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

et al. 2017

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SUMMARY Sophisticated mechanisms that preserve genome integrity are critical to ensure the maintenance of regenerative capacity while preventing transformation of somatic stem cells (SCs), yet little is known about mechanisms regulating genome maintenance in these cells. Here we show that intestinal stem cells (ISCs) induce the Argonaute family protein Piwi in response to JAK/STAT signaling during acute proliferative episodes. Piwi function is critical to ensure heterochromatin maintenance, suppress retrotransposon activation, and prevent DNA damage in homeostasis and under regenerative pressure. Accordingly, loss of Piwi results in loss of actively dividing ISCs and their progenies by apoptosis. We further show that Piwi expression is sufficient to allay age-related retrotransposon expression, DNA damage, apoptosis and mis-differentiation phenotypes in the ISC lineage, improving epithelial homeostasis. Our data identify a role for Piwi in the regulation of somatic SC function and highlight the importance of retrotransposon control in somatic SC maintenance.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

et al. 2017

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“…In other species, piRNAs are produced in specific cell lineages. For example, somatic piRNAs silence transposons in D. melanogaster fat body 8 and brain 9,10 , they are important for stem cell maintenance and regeneration in the planarian Schmidtea mediterranea 11,12 , and they contribute to memory in the central nervous system of the mollusc Aplesia californica 13 .…”

Section: Introductionmentioning

confidence: 99%

Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements

Lewis¹,

Quarles²,

Yang³

et al. 2017

Nat Ecol Evol

229

221

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Summary Paragraph In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were likely present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and mRNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders, scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.

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“…TE expression is upregulated in aging metazoan somatic tissues and in aging yeast, suggesting that TE de-repression is a conserved feature of cellular aging (Maxwell et al 2011;Cecco et al 2013;Li et al 2013;Van Meter et al 2014;Patterson et al 2015;Wood et al 2016). Some studies show that repressing TEs can extend lifespan, thus understanding the mechanisms by which long-lived organisms repress TEs is of interest Jones et al 2016;Wang et al 2011;Cecco et al 2019;Simon et al 2019). Here we show that the PIWI-piRNA pathway represses TEs in the somatic stem cells of the long-lived Hydra.…”

Section: Resultsmentioning

confidence: 99%

“…A prominent feature of somatic aging is the breakdown of heterochromatic domains and expression of transposable elements (TEs), which are typically repressed (López-Otín et al 2013;Cecco et al 2013;Benayoun et al 2018;Jones et al 2016;Li et al 2013;Patterson et al 2015;Hendrickson et al 2018;Sousa-Victor et al 2017). Although TE expression is likely a secondary effect of heterochromatin disruption, mounting evidence suggests that suppressing TE mobilization can extend lifespan Jones et al 2016;Wang et al 2011;Cecco et al 2019;Simon et al 2019). Therefore, it is of interest to understand how long-lived organisms, such as Hydra vulgaris, repress TE expression in somatic cells.…”

Section: Introductionmentioning

confidence: 99%

PIWI-piRNA pathway-mediated transposable element repression inHydrasomatic stem cells

Teefy

Siebert

Cazet

et al. 2019

Preprint

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Transposable elements (TEs) can damage genomes, thus organisms employ a variety of mechanisms to repress TE expression. However, these mechanisms often fail over time leading to de-repression of TEs in aging tissues. The PIWI-piRNA pathway is a small RNA pathway that represses TE expression in the germline of animals. Here we explore the function of the pathway in the epithelial stem cells of Hydra, a long-lived freshwater cnidarian. Hydra have three stem cell populations; endodermal and ectodermal epithelial stem cells are strictly somatic, whereas the interstitial stem cells retain germline competence. In our previous study, we found that the PIWI proteins are expressed in all three Hydra stem cell types. In this study, we focus on the ectodermal and endodermal epithelial stem cells to understand the somatic function of the pathway. We isolated piRNAs from Hydra that lack the interstitial lineage and found that these somatic piRNAs map predominantly to TE transcripts and display the conserved sequence signatures typical of germline piRNAs. Three lines of evidence suggest that the PIWI-piRNA pathway represses TEs in Hydra epithelial stem cells. First, epithelial knockdown of the Hydra PIWI protein hywi resulted in upregulation of TE expression. Second, degradome sequencing revealed evidence of PIWImediated cleavage of TE RNAs in epithelial cells using the ping-pong mechanism. Finally, we demonstrated a direct association between Hywi protein and TE transcripts in epithelial cells using RNA immunoprecipitation. Interestingly, we found that RNAi knockdown of hywi leads to an upregulation of genes involved in innate immunity, which may be in response to TE upregulation; this is consistent with recent studies on TE expression in mammalian cells. Altogether, this study suggests a function for the PIWI-piRNA pathway in maintaining the long-lived somatic cell lineages of Hydra and may point to a broader role for this pathway in protecting somatic tissue from TE-induced damage.

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A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan

Cited by 98 publications

References 41 publications

Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements

PIWI-piRNA pathway-mediated transposable element repression inHydrasomatic stem cells

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