日本的研究人員將小鼠的干細(xì)胞轉(zhuǎn)化成為能夠在活的小鼠體內(nèi)產(chǎn)生卵子的生殖細(xì)胞。這些卵子接著可通過試管受精而產(chǎn)生可存活的后代。這一研究——與已經(jīng)對精子所做的研究工作相映照——可能會開啟關(guān)于雌性生殖細(xì)胞的新的了解的大門并對**某種形式的人類不孕癥提供新的線索。
Mitinori Saitou及其同事以兩類雌性小鼠干細(xì)胞作為開始：胚胎干細(xì)胞（ESCs）——它們來自早期的胚胎并有發(fā)育成為任何胚胎組織類型的潛力——及誘發(fā)的多能干細(xì)胞（iPSCs）——這些細(xì)胞是在成年體細(xì)胞被誘導(dǎo)進(jìn)入多能狀態(tài)時所產(chǎn)生的細(xì)胞。
研究人員對這些細(xì)胞中的一些基因進(jìn)行了修飾，將它們轉(zhuǎn)變成為與原始生殖細(xì)胞非常像的細(xì)胞。他們接著將這些細(xì)胞與雌性小鼠的性腺細(xì)胞共同培養(yǎng)，創(chuàng)造了一個“再造的卵巢”，該再造卵巢接著被移植到某個小鼠的卵巢或腎臟。這些細(xì)胞在那里接著成熟成為充分生長的卵母細(xì)胞。
當(dāng)研究人員分離出這些成熟的卵母細(xì)胞并將其用于小鼠的IVF時，他們制造出了能夠生育的小鼠，從而證明小鼠的ESCs和iPSCs可用來產(chǎn)生具有完全功能的卵母細(xì)胞。
doi: 10.1126/science.1226889
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Offspring from Oocytes Derived from in Vitro Primordial Germ Cell–Like Cells in Mice
Katsuhiko Hayashi, Sugako Ogushi, Kazuki Kurimoto, So Shimamoto, Hiroshi Ohta, Mitinori Saitou
Reconstitution of female germ-cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells and induced pluripotent stem cells in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, undergo X-reactivation, imprint erasure, cyst formation, and exhibit meiotic potential. Upon transplantation under mouse ovarian bursa, PGCLCs in the reconstituted ovaries mature into germinal vesicle-stage oocytes, which then contribute to fertile offspring after in vitro maturation and fertilization. Our culture system serves as a robust foundation for the investigation of key properties of female germ cells, including the acquisition of totipotency, and for the reconstitution of whole female germ-cell development in vitro.
