Polycomb group gene E(z) is required for spermatogonial dedifferentiation in Drosophila adult testis

Dedifferentiation is an important process to replenish lost stem cells during aging or regeneration after injury to maintain tissue homeostasis. Here we report that Enhancer of Zeste [E(z)], a component of the Polycomb Repression Complex 2 (PRC2), is required for the partially differentiated germ cell to dedifferentiate, in order to maintain a stable pool of germline stem cells (GSCs) within the niche microenvironment. During aging, germ cells with reduced E(z) activity have defects in maintaining GSCs, which is not due to increased GSC death or premature differentiation. We found evidence that the decrease of GSCs upon inactivation of E(z) in the germline is likely attributed by defective dedifferentiation. In addition, E(z) mutant germ cells fail to replenish lost GSCs during recovery from genetically manipulated GSC depletion. Together, our data suggest that E(z) acts intrinsically in germ cells for the dedifferentiation process to replenish lost GSCs during both aging and tissue regeneration. Examination of H3K4me3 and RNA polymerase II between E(z) bam double mutant testes and bam mutant testes (submitted in GSE19325 (GSM480446, GSM480449)).

细胞去分化（Dedifferentiation）是机体衰老过程中补充丢失的干细胞，或是损伤后再生阶段维持组织稳态的关键过程。本研究发现，多梳抑制复合体2（Polycomb Repression Complex 2, PRC2）的组分之一Zeste增强子[Enhancer of Zeste, E(z)]，是部分分化的生殖细胞发生去分化、以维持干细胞龛微环境内生殖系干细胞（germline stem cells, GSCs）稳定储备库所必需的因子。在衰老进程中，E(z)活性降低的生殖细胞无法维持GSC稳态，该缺陷并非由GSC死亡增加或过早分化所导致。我们的研究结果显示，生殖细胞中E(z)失活引发的GSC数量减少，其潜在原因很可能是去分化过程存在缺陷。此外，在经遗传操作耗竭GSC后的恢复阶段，E(z)突变的生殖细胞无法补充丢失的GSC。综上，本研究数据表明，在衰老与组织再生两种场景下，E(z)可在生殖细胞内以细胞自主性方式介导去分化过程，从而补充丢失的GSC。我们还对E(z) bam双突变睾丸与bam单突变睾丸中的H3K4me3与RNA聚合酶II进行了检测，相关数据已提交至GSE19325（包含GSM480446、GSM480449）。