日本理化研究所科研人员在7日的美国《细胞—干细胞》(Cell Stem cell)杂志网络版上报告说,他们借助用克隆动物培育克隆动物的“再克隆”技术,成功地用一只实验鼠培育出了26代共598只实验鼠。
克隆技术面临的一大课题是克隆动物生育率低下,繁殖代数越多,生育率越低。迄今为止,实验鼠繁殖6代、牛繁殖两代就达到了极限。一旦提供可供克隆的细胞的动物死亡,遗传信息就会断绝。
理化研究所研究员若山照彦率领的研究小组2005年曾发现,在培育克隆实验鼠的时候,将移植了细胞核的卵细胞浸入一种名为“曲古抑菌素A”的“组蛋白去乙酰化酶抑制剂”中,生育率就会提高。研究小组不断改良技术,成功培育了26代实验鼠,且生育率最高达到约15%。
研究发现,克隆的实验鼠很健康,繁殖能力和寿命与一般实验鼠也没有区别。研究人员认为,这说明再克隆可以无限持续下去。
由于克隆动物遗传特性相同,所以再克隆技术有望用于肉质好的牛等良种家畜的大规模生产及濒危物种的保护。
PRDM14 Ensures Naive Pluripotency through Dual Regulation of Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells
Masashi Yamaji, Jun Ueda, Katsuhiko Hayashi, Hiroshi Ohta, Yukihiro Yabuta, Kazuki Kurimoto
In serum, mouse embryonic stem cells (mESCs) fluctuate between a naive inner cell mass (ICM)-like state and a primed epiblast-like state, but when cultured with inhibitors of the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i), they are harnessed exclusively in a distinct naive pluropotent state, the ground state, that more faithfully recapitulates the ICM. Understanding the mechanism underlying this naive pluripotent state will be critical for realizing the full potential of ESCs. We show here that PRDM14, a PR-domain-containing transcriptional regulator, ensures naive pluripotency through a dual mechanism: antagonizing activation of the fibroblast growth factor receptor (FGFR) signaling by the core pluripotency transcriptional circuitry, and repressing expression of de novo DNA methyltransferases that modify the epigenome to a primed epiblast-like state. PRDM14 exerts these effects by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.