Integrin restriction by miR‐34 protects germline progenitors from cell death during aging

Author:

Perry Noam1,Braun Racheli12,Ben‐Hamo‐Arad Aya1,Kanaan Diana1,Arad Tal1,Porat‐Kuperstein Lilach1,Toledano Hila1ORCID

Affiliation:

1. Department of Human Biology, Faculty of Natural Sciences University of Haifa Haifa Israel

2. Biomedical Engineering Faculty Technion IITs Haifa Israel

Abstract

AbstractDuring aging, regenerative tissues must dynamically balance the two opposing processes of proliferation and cell death. While many microRNAs are differentially expressed during aging, their roles as dynamic regulators of tissue regeneration have yet to be described. We show that in the highly regenerative Drosophila testis, miR‐34 levels are significantly elevated during aging. miR‐34 modulates germ cell death and protects the progenitor germ cells from accelerated aging. However, miR‐34 is not expressed in the progenitors themselves but rather in neighboring cyst cells that kill the progenitors. Transcriptomics followed by functional analysis revealed that during aging, miR‐34 modifies integrin signaling by limiting the levels of the heterodimeric integrin receptor αPS2 and βPS subunits. In addition, we found that in cyst cells, this heterodimer is essential for inducing phagoptosis and degradation of the progenitor germ cells. Together, these data suggest that the miR‐34—integrin signaling axis acts as a sensor of progenitor germ cell death to extend progenitor functionality during aging.

Publisher

Wiley

Reference49 articles.

1. miR-34: from bench to bedside

2. The haemopoietic stem cell: Between apoptosis and self renewal;Alenzi F. Q.;The Yale Journal of Biology and Medicine,2009

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