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Generation of marmoset primordial germ cell-like cells under chemically defined conditions.
Life Science Alliance ( IF 4.4 ) Pub Date : 2024-03-18 , DOI: 10.26508/lsa.202302371
Julia Kurlovich 1 , Ignacio Rodriguez Polo 1, 2, 3 , Oleksandr Dovgusha 1 , Yuliia Tereshchenko 2, 4 , Carmela Rieline V Cruz 1 , Rüdiger Behr 2, 4 , Ufuk Günesdogan 1, 5
Affiliation  

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 Callithrix jacchus (cj). 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.

中文翻译:

在化学限定的条件下产生狨猴原始生殖细胞样细胞。

原始生殖细胞 (PGC) 是精子和卵母细胞的胚胎前体,可跨代传递遗传/表观遗传信息。小鼠 PGC 和随后的配子发育可以在体外完全重建,为生物医学研究中的生殖细胞研究开辟新途径。然而,PGC 在啮齿动物和人类之间表现出分子差异。因此,为了建立与人类密切相关的体外系统,我们研究了普通狨猴Callithrix jacchus ( cj )体内和体外PGC的发育。胚胎第 74 天的性腺 cjPGC 表达 SOX17、AP2Ɣ、BLIMP1、NANOG 和 OCT4A,这让人想起人类 PGC。我们从胎儿和出生后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 在限定且无饲养层的条件下培养,可分化为中内胚层前体,随后分化为 cjPGC 样细胞 (cjPGCLC),其转录组与人类 PGC/PGCLC 相似。我们的结果不仅为在实验控制条件下体外研究非人类灵长类动物的 PGC 发育铺平了道路,而且还为在未来的研究中获得功能性狨猴配子提供了机会。
更新日期:2024-03-18
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