Re: 用iPS 複製動物? (2)
In general, the success rate of cloned mice from ES cell nuclei is known to
be higher than that of cloned mice from somatic cell nuclei [01, 02],
suggesting that the undifferentiated state of donor cells, or somatic stem
cells, may increase cloning efficiency.
[review] Teruhiko WAKAYAMA. Production of Cloned Mice and ES Cells from Adult
Somatic Cells by Nuclear Transfer: How to Improve Cloning Efficiency? J.
Reprod. Dev. 53: 13-26, 2007.
[01] Wakayama T. et al. Mice cloned from embryonic stem cells. Proc Natl Acad
Sci USA 1999; 96: 14984-14989.
[02] Rideout W. M. et al. Generation of mice from wild-type and targeted ES
cells by nuclear cloning. Nat Genet 2000;24: 109-110.
這是產生第一隻複製鼠的若山照彥所寫的review,他說胚胎幹細胞的複製效率會比體細胞
好,但他並沒有說donor cells用成體幹細胞會比用體細胞好,胚胎幹細胞跟幹細胞是不
一樣的。因為有一篇論文提到,用終極分化的顆粒細胞產製複製囊胚的效率比用成體幹細
胞好(34 vs 10%)
[paper] Sung L. Y. et al. 2006. Differentiated cells are more efficient than
adult stem cells for cloning by somatic cell nuclear transfer. Nat. Genet.
38:1323-1328.
另外,使用iPS cells做為複製動物的核捐贈細胞,複製效率是有可能比體細胞來的好。
但是,可能沒有人做的原因可能是下面的幾個原因:
第一,iPS有4個基因受到受到反轉錄病毒修飾重新表現,你拿iPS做複製,所產生動物基
因跟之前的細胞的基因會不相同,這就不叫做複製動物了吧。
第二點就是產生出iPS cells的目的就是不必經過複雜的顯微注射過程就可以產生出病人
專一的幹細胞,如果拿iPS cells作為供核細胞來進行複製,那就失去了產生iPS原本的意
義。
第三點,目前iPS cells的功能幾乎可媲美胚胎幹細胞,具有性腺遺傳的功能,可以產生
出嵌合小鼠[03, 04],所以可能可以與4N的囊胚做嵌合的方式來產生複製動物,比較簡單
也比較容易成功,而不需要用體細胞核轉製的方式來做。
[03] Okita, K. et al. 2007. Generation of germline- competentinduced
pluripotent stem cells. Nature 448:313-317.
[04] Wernig, M. et al. 2007. In vitro reprogramming of fibroblasts into a
pluripotent ES-cell-like state. Nature 448:318-324.
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