Data from: miR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression

Ageing is characterized by a decline in stem cell functionality leading to dampened tissue regeneration. While the expression of microRNAs across multiple species is markedly altered with age, the mechanism by which they govern stem cell-sustained tissue regeneration is unknown. We report that in the Drosophila testis, the conserved miR-9a is expressed in germline stem cells and its levels are significantly elevated during ageing. Transcriptome and functional analyses show that miR-9a directly regulates the expression of the adhesion molecule N-cadherin (N-cad). miR-9a null mutants maintain a higher number of stem cells even in the aged tissue. Remarkably, this rise fails to improve tissue regeneration and results in reduced male fertility. Similarly, overexpression of N-cad also results in elevated stem cell number and decreased regeneration. We propose that miR-9a downregulates N-cad to enable adequate detachment of stem cells toward differentiation, thus providing the necessary directionality toward terminal differentiation and spermatogenesis.衰老以干细胞功能衰退为核心特征，进而引发组织再生能力减弱。尽管多个物种中的微小RNA（microRNAs）表达水平随年龄增长发生显著改变，但这类RNA调控干细胞维持组织再生的具体机制仍不明晰。本研究发现，在果蝇（Drosophila）睾丸中，进化保守的miR-9a在生殖系干细胞中表达，且其表达水平在衰老进程中显著升高。转录组与功能分析表明，miR-9a可直接调控黏附分子N-钙黏蛋白（N-cadherin, N-cad）的表达。miR-9a敲除突变体即使在衰老组织中仍可维持更多的干细胞数量。值得注意的是，干细胞数量的提升并未改善组织再生能力，反而导致雄性生育能力下降。同样，N-cad过表达也会使干细胞数量增加，同时降低组织再生能力。本研究提出，miR-9a通过下调N-cad的表达，使干细胞能够充分脱离并启动分化，从而为终末分化与精子发生提供必要的方向性调控。