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Research Paper|Volume 11, Issue 3|pp 855—873

Lin28 is a critical factor in the function and aging of Drosophila testis stem cell niche

Perinthottathil Sreejith1,2, Wijeong Jang1, Van To1, Yong Hun Jo3, Benoit Biteau2, Changsoo Kim1
  • 1School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of Korea
  • 2Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA
  • 3Division of Plant Biotechnology, Institute of Environmentally-Friendly Agriculture (IEFA), College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea
Received: October 18, 2018Accepted: January 5, 2019Published: February 4, 2019
https://doi.org/10.18632/aging.101765

Copyright: © 2019 Sreejith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Age-related decline in stem cell function is observed in many tissues from invertebrates to humans. While cell intrinsic alterations impair stem cells, aging of the stem cell niche also significantly contributes to the loss of tissue homeostasis associated with reduced regenerative capacity. Hub cells, which constitute the stem cell niche in the Drosophila testis, exhibit age-associated decline in number and activities, yet underlying mechanisms are not fully understood. Here we show that Lin28, a highly conserved RNA binding protein, is expressed in hub cells and its expression dramatically declines in old testis. lin28 mutant testes exhibit hub cell loss and defective hub architecture, recapitulating the normal aging process. Importantly, maintained expression of Lin28 prolongs hub integrity and function in aged testes, suggesting that Lin28 decline is a driver of hub cell aging. Mechanistically, the level of unpaired (upd), a stem cell self-renewal factor, is reduced in lin28 mutant testis and Lin28 protein directly binds and stabilizes upd transcripts, in a let-7 independent manner. Altogether, our results suggest that Lin28 acts to protect upd transcripts in hub cells, and reduction of Lin28 in old testis leads to decreased upd levels, hub cell aging and loss of the stem cell niche.