科技日報(bào)訊據(jù)英國《自然》期刊本周發(fā)表的一項(xiàng)研究稱，科學(xué)家證實(shí)成年體細(xì)胞可在活鼠體內(nèi)被重新編程為多能干細(xì)胞。在這之前,，學(xué)界一直不清楚生物體內(nèi)環(huán)境是否適合重編程，而最新研究表明這是可行的,。這一發(fā)現(xiàn)將有助于提高干細(xì)胞的可塑性,，并有望為再生醫(yī)學(xué)帶來新的應(yīng)用。
細(xì)胞核重編程就像細(xì)胞層面的“返老還童”過程,。是將已經(jīng)分化了的成年體細(xì)胞進(jìn)行誘導(dǎo),，讓其重新回到發(fā)育早期多能性干細(xì)胞狀態(tài)。早期科學(xué)家曾認(rèn)為這是一個不可逆的過程,，成熟的,、專門的細(xì)胞不可能重新編程，反過來逆分化變成干細(xì)胞,，但日本醫(yī)學(xué)教授山中伸彌和英國發(fā)育生物學(xué)家約翰·戈登扭轉(zhuǎn)了這種觀點(diǎn),，他二人也因此獲得2012年諾貝爾生理學(xué)或醫(yī)學(xué)獎。
細(xì)胞“再編程”的突破雖然在實(shí)驗(yàn)上簡單,、易重復(fù),，但效果卻是里程碑式的，但目前人們還不清楚生物體內(nèi)環(huán)境是否適合重編程,。
而此次西班牙國家癌癥研究中心曼努爾·塞拉諾及其同事在研究中發(fā)現(xiàn),，用來制作多能干細(xì)胞的傳統(tǒng)“誘導(dǎo)配方”,，即使用Oct4,、Sox2、Klf4和c-Myc四種誘導(dǎo)因子,，不但可用于培養(yǎng)皿中,，更可用于活鼠體內(nèi)。他們檢驗(yàn)了從腎,、胃,、小腸和胰腺抽取出來的細(xì)胞，發(fā)現(xiàn)全部擁有被編程過的跡象,。
研究同時發(fā)現(xiàn),，在活鼠體內(nèi)產(chǎn)生的誘導(dǎo)性多能干細(xì)胞（簡稱iPS細(xì)胞）比在培養(yǎng)皿中產(chǎn)生的iPS細(xì)胞更接近胚胎干細(xì)胞（簡稱ES細(xì)胞）。此外，在活鼠體內(nèi)產(chǎn)生的iPS細(xì)胞比平常的iPS細(xì)胞或ES細(xì)胞擁有更大的分化潛力,，這表明在生物體內(nèi)進(jìn)行重編程,，將有助于提高干細(xì)胞的可塑性。
這種iPS細(xì)胞將可以分化成不同成熟細(xì)胞類型,，若嚴(yán)格控制其人工培養(yǎng)過程,，可用于開發(fā)新的治療模式。同時,，上升到哺乳動物層面,，細(xì)胞核重編程也是正常受精胚胎和克隆胚胎發(fā)育過程中的一個重要特性，可對表觀遺傳學(xué)特征,，包括染色質(zhì)重塑,、組蛋白修飾、DNA甲基化,、印記基因表達(dá)等進(jìn)行重新編寫,，進(jìn)一步了解這一機(jī)制也將為生物醫(yī)學(xué)領(lǐng)域帶來無數(shù)可能。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Nature doi:10.1038/nature12586
Reprogramming in vivo produces teratomas and iPS cells with totipotency features
María Abad, Lluc Mosteiro, Cristina Pantoja, Marta Cañamero, Teresa Rayon, Inmaculada Ors, Osvaldo Graña, Diego Megías, Orlando Domínguez, Dolores Martínez, Miguel Manzanares, Sagrario Ortega & Manuel Serrano
Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues. Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed in vivo. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these in vivo generated iPS cells are closer to embryonic stem cells (ES cells) than standard in vitro generated iPS cells. Moreover, in vivo iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming in vivo is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine.
