https://ror.org/01y9bpm73 Göttingen Center for Molecular Biosciences, Department of Developmental Biology, University of Göttingen, Göttingen, Germany.
German Primate Center-Leibniz Institute for Primate Research, Research Platform Degenerative Diseases, Göttingen, Germany.
Life Sci Alliance. 2024 Mar 18;7(6). doi: 10.26508/lsa.202302371. Print 2024 Jun.
Primordial germ cells (PGCs) are the embryonic precursors of sperm and oocytes, which transmit genetic/epigenetic information across generations. Mouse PGC and subsequent gamete development can be fully reconstituted in vitro, opening up new avenues for germ cell studies in biomedical research. However, PGCs show molecular differences between rodents and humans. Therefore, to establish an in vitro system that is closely related to humans, we studied PGC development in vivo and in vitro in the common marmoset monkey (). Gonadal cjPGCs at embryonic day 74 express SOX17, AP2Ɣ, BLIMP1, NANOG, and OCT4A, which is reminiscent of human PGCs. We established transgene-free induced pluripotent stem cell (cjiPSC) lines from foetal and postnatal fibroblasts. These cjiPSCs, cultured in defined and feeder-free conditions, can be differentiated into precursors of mesendoderm and subsequently into cjPGC-like cells (cjPGCLCs) with a transcriptome similar to human PGCs/PGCLCs. Our results not only pave the way for studying PGC development in a non-human primate in vitro under experimentally controlled conditions, but also provide the opportunity to derive functional marmoset gametes in future studies.
原始生殖细胞 (PGCs) 是精子和卵子的胚胎前体,它们将遗传/表观遗传信息传递给后代。小鼠 PGC 及其随后的配子发生可以在体外完全重建,为生殖细胞在生物医学研究中的研究开辟了新的途径。然而,PGCs 在啮齿动物和人类之间存在分子差异。因此,为了建立与人类密切相关的体外系统,我们研究了食蟹猴 () 体内和体外的 PGC 发育。在胚胎第 74 天,性腺 cjPGCs 表达 SOX17、AP2Ɣ、BLIMP1、NANOG 和 OCT4A,这让人联想到人类 PGC。我们从胎儿和成纤维细胞中建立了无转基因诱导多能干细胞 (cjiPSC) 系。这些 cjiPSC 在定义和无饲养层的条件下培养,可以分化为中胚层前体,随后分化为具有类似于人类 PGC/PGCLCs 转录组的 cjPGC 样细胞 (cjPGCLCs)。我们的研究结果不仅为在实验控制条件下研究非人类灵长类动物体外 PGC 发育铺平了道路,而且还为未来研究中获得功能性狨猴配子提供了机会。