Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis.
Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis.
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DOI：
10.1126/sciadv.1602179
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发表时间：
2017-05
期刊：
影响因子：
13.6
通讯作者：
Koshimoto C
中科院分区：
文献类型：
--
作者：
Honda A;Choijookhuu N;Izu H;Kawano Y;Inokuchi M;Honsho K;Lee AR;Nabekura H;Ohta H;Tsukiyama T;Ohinata Y;Kuroiwa A;Hishikawa Y;Saitou M;Jogahara T;Koshimoto C
Tokudaia osimensis表现出高度的性可塑性，通过雌性体细胞可以转化为雄性生殖细胞。在哺乳动物中，Y染色体严格影响雄性生殖细胞的维持。几乎所有的哺乳动物物种都需要基因贡献者来产生睾丸。濒危物种Tokudaia osimensis具有独特的性染色体组成XO/XO，雌雄之间的遗传差异尚未得到证实。尽管在T. osimensis中可能存在一种独特的性别决定机制，但很难对这种稀有动物物种进行彻底的研究。为了阐明T. osimensis的性别决定机制，并找到防止其可能灭绝的策略，我们建立了诱导多能干细胞（iPSCs），并以小鼠为宿主和受体获得了种间嵌合体。生成的iPSCs被认为处于所谓的“真实naïve”状态，T. osimensis iPSCs可能作为种间嵌合体在活体动物的几种不同组织和细胞中发挥作用。令人惊讶的是，雌性T. osimensis iPSCs不仅在种间小鼠卵巢中形成雌性生殖系，而且还分化为精子细胞和精子细胞，并在成年种间小鼠睾丸中存活。因此，T. osimensis细胞具有高度的性可塑性，通过雌性体细胞可以转化为雄性种系细胞。这些发现表明T. osimensis细胞具有灵活性，可以使其生殖细胞性别适应性腺生态位。本研究表明，iPSCs的使用可能会降低濒危物种的灭绝风险。
Tokudaia osimensis exhibits high sexual plasticity, through which female somatic cells can be converted to male germline cells. In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis, has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis, it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T. osimensis and to find a strategy to prevent its possible extinction, we have established induced pluripotent stem cells (iPSCs) and derived interspecific chimeras using mice as the hosts and recipients. Generated iPSCs are considered to be in the so-called “true naïve” state, and T. osimensis iPSCs may contribute as interspecific chimeras to several different tissues and cells in live animals. Surprisingly, female T. osimensis iPSCs not only contributed to the female germ line in the interspecific mouse ovary but also differentiated into spermatocytes and spermatids that survived in the adult interspecific mouse testes. Thus, T. osimensis cells have high sexual plasticity through which female somatic cells can be converted to male germline cells. These findings suggest flexibility in T. osimensis cells, which can adapt their germ cell sex to the gonadal niche. The probable reduction of the extinction risk of an endangered species through the use of iPSCs is indicated by this study.