來自北卡羅來那州維克森林大學(xué)（Wake Forest University）醫(yī)學(xué)院,，再生醫(yī)學(xué)研究院，德州理工大學(xué),，先進(jìn)細(xì)胞技術(shù)公司等處的研究人員發(fā)現(xiàn)雖然克隆人類胚胎能表達(dá)實(shí)現(xiàn)多能性需要的各種基因,，但是動物－人類的雜合細(xì)胞卻不具有多能性，這對于從治療性克隆中分離人類胚胎干細(xì)胞意義重大,，也是繼黃禹錫的造假克隆實(shí)驗(yàn)之后的一項(xiàng)重大研究成果,。這一研究成果公布在Cloning and Stem Cells雜志上。
領(lǐng)導(dǎo)這一研究的是先進(jìn)細(xì)胞技術(shù)公司ACT的研究總監(jiān)Robert Lanza,，他表示,，“這些卵細(xì)胞不能被重新編程”，人類－動物雜合胚胎無法進(jìn)行多能性分化,。
由于人類卵細(xì)胞的缺乏,，許多研究人員希望能通過將人類細(xì)胞核注射到動物卵細(xì)胞中，獲得病人特異性的人類胚胎干細(xì)胞,，雖然這項(xiàng)工作目前并沒有得到美國政府的資助,，但是在世界各地的許多實(shí)驗(yàn)室中都開展了相關(guān)內(nèi)容的研究，其中也包括允許進(jìn)行動物－人類雜合胚胎研究的英國科學(xué)家,。
Lanza博士和他的同事分析了體外培養(yǎng)的人－人克隆,，人－牛克隆,，人－大鼠克?。ㄖ饕侄螢楹艘浦布夹g(shù)）的早期胚胎的全基因組表達(dá)情況，結(jié)果他們發(fā)現(xiàn)雖然種間雜合的胚胎看起來和人類胚胎相似,，但是它們并不具有相同的表達(dá)模式,。
在人類－動物雜合胚胎中，有大約2300多個基因差異表達(dá),，其中大部分是負(fù)調(diào)控基因,，而且引起科學(xué)家注意的是，只有人類胚胎能增加關(guān)鍵全能性基因： Oct-4, Sox-2和nanog的表達(dá),，“這些細(xì)胞不會開啟正常的基因,，相反，它們會將這些基因關(guān)閉或沉默”,，Lanza表示,。
Lanza的這一研究成果除了否定了雜合胚胎,，也為人類治療性克隆能獲得定制的胚胎干細(xì)胞提供了新的證據(jù)，“這是第一次,，不僅發(fā)現(xiàn)了細(xì)胞重新編程需要的關(guān)鍵的基因,，而且捐獻(xiàn)DNA重新編程途徑與正常胚胎相同。”
而在08年發(fā)表在同一雜志上的,，來自中國上海交通大學(xué)的盛輝（Hui Sheng,，音譯）等人的研究成果則與之不同，盛輝等人發(fā)現(xiàn)在人－牛雜合胚胎晚期,，有5個多能性相關(guān)基因活躍,，其中包括Lanza研究組中分析的3個。Lanza則對于中國的這一研究結(jié)果不以為然,，對Sheng的研究組的研究成果表示懷疑,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cloning and Stem Cells. ahead of print. doi:10.1089/clo.2009.0004.
Reprogramming of Human Somatic Cells Using Human and Animal Oocytes
Young Chung, Colin E. Bishop, Nathan R. Treff, Stephen J. Walker, Vladislav M. Sandler, Sandy Becker, Irina Klimanskaya, Wan-Song Wun, Randall Dunn, Rebecca M. Hall, Jing Su, Shi-Jiang Lu, Marc Maserati, Young-Ho Choi, Richard Scott, Anthony Atala, Ralph Dittman, Robert Lanza.
There is renewed interest in using animal oocytes to reprogram human somatic cells. Here we compare the reprogramming of human somatic nuclei using oocytes obtained from animal and human sources. Comparative analysis of gene expression in morula-stage embryos was carried out using single-embryo transcriptome amplification and global gene expression analyses. Genomic DNA fingerprinting and PCR analysis confirmed that the nuclear genome of the cloned embryos originated from the donor somatic cell. Although the human–human, human–bovine, and human–rabbit clones appeared morphologically similar and continued development to the morula stage at approximately the same rate (39, 36, and 36%, respectively), the pattern of reprogramming of the donor genome was dramatically different. In contrast to the interspecies clones, gene expression profiles of the human–human embryos showed that there was extensive reprogramming of the donor nuclei through extensive upregulation, and that the expression pattern was similar in key upregulation in normal control embryos. To account for maternal gene expression, enucleated oocyte transcriptome profiles were subtracted from the corresponding morula-stage embryo profiles. t-Test comparisons (median-normalized data @ fc > 4; p < 0.005) between human in vitro fertilization (IVF) embryos and human–bovine or human–rabbit interspecies somatic cell transfer (iSCNT) embryos found between 2400 and 2950 genes that were differentially expressed, the majority (60–70%) of which were downregulated, whereas the same comparison between the bovine and rabbit oocyte profiles found no differences at all. In contrast to the iSCNT embryos, expression profiles of human–human clones compared to the age-matched IVF embryos showed that nearly all of the differentially expressed genes were upregulated in the clones. Importantly, the human oocytes significantly upregulated Oct-4, Sox-2, and nanog (22-fold, 6-fold, and 12-fold, respectively), whereas the bovine and rabbit oocytes either showed no difference or a downregulation of these critical pluripotency-associated genes, effectively silencing them. Without appropriate reprogramming, these data call into question the potential use of these discordant animal oocyte sources to generate patient-specific stem cells.
