Generation of germline-competent rat induced pluripotent stem cells.
Generation of germline-competent rat induced pluripotent stem cells.
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DOI：
10.1371/journal.pone.0022008
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Nakauchi H
中科院分区：
文献类型：
--
作者：
Hamanaka S;Yamaguchi T;Kobayashi T;Kato-Itoh M;Yamazaki S;Sato H;Umino A;Wakiyama Y;Arai M;Sanbo M;Hirabayashi M;Nakauchi H
近年来，大鼠多能干细胞技术取得了令人瞩目的进展。特别突出的是大鼠胚胎干细胞（ESCs） （rESCs）可以促进种系传播，允许产生基因修饰的大鼠，就像现在使用小鼠ESCs （mESCs）或小鼠诱导多能干细胞（iPSCs; miPSCs）一样。然而，关于大鼠iPSCs （riPSCs）是否能促进生殖细胞的测定尚未发表。在这里，我们报道了riPSCs的种系能力。我们通过将三种小鼠重编程因子（Oct3/4、Klf4和Sox2）转导到大鼠体细胞中，然后在外源性大鼠白血病抑制因子（rLIF）和特异性抑制GSK3、MEK和FGF受体酪氨酸激酶的小分子存在下培养，生成了riPSCs。我们发现，像rESCs一样，我们的riPSCs可以促进种系传播。此外，通过对小鼠-大鼠种间嵌合体的睾丸进行免疫染色，我们发现riPSCs可以促进小鼠（大鼠-小鼠种间嵌合体）和种间种系的胚胎发育和嵌合体的形成。我们的数据清楚地表明，仅使用三种重编程因子（Oct3/4， Klf4和Sox2）就可以将大鼠体细胞重编程为基态。我们生成的riPSCs在大鼠-大鼠种内或小鼠-大鼠种间嵌合体中均表现出种系传播。
Recent progress in rat pluripotent stem cell technology has been remarkable. Particularly salient is the demonstration that embryonic stem cells (ESCs) in the rat (rESCs) can contribute to germline transmission, permitting generation of gene-modified rats as is now done using mouse ESCs (mESCs) or mouse induced pluripotent stem cells (iPSCs; miPSCs). However, determinations of whether rat iPSCs (riPSCs) can contribute to germ cells are not published. Here we report the germline competency of riPSCs. We generated riPSCs by transducing three mouse reprogramming factors (Oct3/4, Klf4, and Sox2) into rat somatic cells, followed by culture in the presence of exogenous rat leukemia inhibitory factor (rLIF) and small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. We found that, like rESCs, our riPSCs can contribute to germline transmission. Furthermore we found, by immunostaining of testis from mouse-rat interspecific chimeras with antibody against mouse vasa homolog, that riPSCs can contribute to embryonic development with chimera formation in mice (rat-mouse interspecific chimeras) and to interspecific germlines. Our data clearly demonstrate that using only three reprogramming factors (Oct3/4, Klf4, and Sox2) rat somatic cells can be reprogrammed into a ground state. Our generated riPSCs exhibited germline transmission in either rat-rat intraspecific or mouse-rat interspecific chimeras.
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