Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

Publication date: 12 September 2017
Source:Cell Reports, Volume 20, Issue 11
Author(s): Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T. Madden, Victoria V. Lunyak, Heinrich Jasper
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 the 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 they highlight the importance of retrotransposon control in somatic SC maintenance.

Graphical abstract

Teaser

Stem cell function depends on mechanisms that ensure the maintenance of genome integrity. Using the Drosophila intestine as a model, Sousa-Victor et al. identify Piwi as a regulator of somatic stem cell genomic integrity, required for long-term maintenance and function of ISCs, and they find that it can allay age-related stem cell dysfunction.


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