College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, No. 3rd, Taicheng Road, Yangling, 712100, Shaanxi, China.
Key Laboratory for Mammalian Reproductive Biology and Biotechnology, Ministry of Education, Inner Mongolia University, Hohhot, 010021, China.
Mol Cell Biochem. 2021 Feb;476(2):1123-1134. doi: 10.1007/s11010-020-03977-3. Epub 2020 Nov 16.
Double sex and mab-3 related transcription factor 1 (DMRT1) encodes a double sex/mab-3 (DM) domain, which is the most conserved structure that involved in sex determination both in vertebrates and invertebrates. This study revealed important roles of DMRT1 in maintaining self-renewal of male germline stem cells (mGSCs). Our results showed that insufficient expression of DMRT1 in mice testes resulted in decreased number of spermatogonial cells and collapse of testicular niche in vivo. Self-renewal and proliferation of mGSCs were inhibited. Based on the bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (co-IP) assay, it was finally revealed that the interaction between DMRT1 and promyelocytic leukemia zinc finger (PLZF) protein was essential for maintaining self-renewal of mGSCs. Moreover, BTB domain of PLZF, DM and DMRT1 domain of DMRT1 were indispensable in mGSC, which were responsible for preserving the quantity of germ cells. Our research provided a new scientific basis for studying the mechanism of self-renewal and spermatogenesis in goat mGSCs.
双性和 mab-3 相关转录因子 1(DMRT1)编码双性/mab-3(DM)结构域,该结构域在脊椎动物和无脊椎动物的性别决定中是最保守的结构。本研究揭示了 DMRT1 在维持雄性生殖干细胞(mGSCs)自我更新中的重要作用。我们的结果表明,小鼠睾丸中 DMRT1 表达不足导致精原细胞数量减少,体内睾丸龛位崩溃。mGSCs 的自我更新和增殖受到抑制。基于双分子荧光互补(BiFC)和免疫共沉淀(co-IP)实验,最终揭示了 DMRT1 和早幼粒细胞白血病锌指(PLZF)蛋白之间的相互作用对于维持 mGSCs 的自我更新是必不可少的。此外,PLZF 的 BTB 结构域、DMRT1 的 DM 结构域和 DMRT1 的 DMRT1 结构域在 mGSCs 中是不可或缺的,它们负责维持生殖细胞的数量。我们的研究为研究山羊 mGSCs 的自我更新和精子发生机制提供了新的科学依据。