nature

当前位置: Nature » 细胞生物学 » 正文

美国科学家利用细胞重组技术成功生成胚胎干细胞

摘要 : 美国俄勒冈健康与科学大学 Shoukhrat Mitalipov 领导的研究团队利用处于细胞“分裂间期”阶段的2-细胞胚胎的细胞质,成功地生成了源自成年小鼠体细胞的胚胎干细胞。相关文章发表于2014年3月26日的《Nature》杂志上。

 美国俄勒冈健康与科学大学 Shoukhrat Mitalipov 领导的研究团队利用处于细胞“分裂间期”阶段的2-细胞胚胎的细胞质,成功地生成了源自成年小鼠体细胞的胚胎干细胞。相关文章发表于2014年3月26日的《Nature》杂志上。

Nature:美国科学家利用细胞重组技术成功生成胚胎干细胞

这些研究成果对于生成患者匹配的人类胚胎干细胞,满足再生医学需求这一学科领域将产生重大的影响。人类胚胎干细胞能够转变为身体的所有细胞类型。科学家们认为,通过替代损伤或疾病破坏的细胞,干细胞治疗有望在某一天治愈或治疗从帕金森病、心脏病到脊髓损伤等许多不同的疾病。

如果在小鼠身上取得的这些新研究结果也能适用于人类,其有可能会大大推动研究努力生成满足再生治疗需求的人类胚胎干细胞。由于 Mitalipov 研究小组利用来进行重编程的胚胎细胞是处于“分裂间期”的细胞,相比于供应短缺的常规卵细胞更容易获取。科学家们过去认为,只能利用分裂中期的卵子细胞质才能生成胚胎干细胞。

利用体细胞核移植(somatic Cell nuclear transfer,SCNT)来生成胚胎干细胞,首先需将来自成体细胞的细胞核转移到未受精卵细胞的细胞质中,随后细胞质结构会“重编程”细胞核,细胞则会转变为能够生成身体所有细胞类型的胚胎干细胞。

Mitalipov 表示:“一直以来人们认为这种重编程能力以分裂中期作为终点。我们的研究显示甚至在分裂间期这一后期的胚胎细胞细胞质中仍然保有这种重编程能力。似乎一些因子在继续起作用,它们能够有效地重编程细胞——就像是它们在分裂中期所做的那样。”

许多科学家曾试图用分裂间期细胞质来重编程细胞。 Mitalipov 和他的同事们通过小心地同步成体细胞核与受体胚胎细胞质的细胞周期取得了成功。 Mitalipov 表示,两者都必须处于各自细胞周期的几乎同一点,这一过程才会起作用。

2013 年,Mitalipov 成功利用克隆技术制造出了人类胚胎干细胞,向培育用于疾病治疗的替代组织迈进了一步,同时也可能加速克隆人类婴儿所需技术的到来。

原文摘要:

Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos

Eunju Kang, Guangming Wu, Hong Ma, Ying Li, Rebecca Tippner-Hedges, Masahito Tachibana, Michelle Sparman, Don P. Wolf, Hans R. Schöler & Shoukhrat Mitalipov

Successful mammalian cloning using somatic cell nuclear transfer (SCNT) into unfertilized, me-taphase II (MII)-arrested oocytes attests to the cytoplasmic presence of reprogramming factors capable of inducing totipotency in somatic cell nuclei. However, these poorly defined maternal factors presumably decline sharply after fertilization, as the cytoplasm of pronuclear-stage zygotes is reportedly inactive. Recent evidence suggests that zygotic cytoplasm, if maintained at me-taphase, can also support derivation of embryonic stem (ES) cells after SCNT, albeit at low efficiency. This led to the conclusion that critical oocyte reprogramming factors present in the me-taphase but not in the interphase cytoplasm are ‘trapped’ inside the nucleus during interphase and effectively removed during enucleation. Here we investigated the presence of reprogramming activity in the cytoplasm of interphase two-cell mouse embryos (I2C). First, the presence of candidate reprogramming factors was documented in both intact and enucleated me-taphase and interphase zygotes and two-cell embryos. Consequently, enucleation did not provide a likely explanation for the inability of interphase cytoplasm to induce reprogramming. Second, when we carefully synchronized the cell cycle stage between the transplanted nucleus (ES cell, fetal fibroblast or terminally differentiated cumulus cell) and the recipient I2C cytoplasm, the reconstructed SCNT embryos developed into blastocysts and ES cells capable of contributing to traditional germline and tetraploid chimaeras. Last, direct transfer of cloned embryos, reconstructed with ES cell nuclei, into recipients resulted in live offspring. Thus, the cytoplasm of I2C supports efficient reprogramming, with cell cycle synchronization between the donor nucleus and recipient cytoplasm as the most critical parameter determining success. The ability to use interphase cytoplasm in SCNT could aid efforts to generate autologous human ES cells for regenerative applications, as donated or discarded embryos are more accessible than unfertilized MII oocytes.

来源: 测序中国 浏览次数:179

热门文章TOP

RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.