Manuel Serrano 及同事首次發現,體細胞被經典「Yamanaka因子」Oct4、Sox2、Klf4和c-Myc重新編程為具有多能性的過程可以在活體中實現。對從小鼠的胃、小腸、胰腺和腎臟細胞在活體中誘導生成的「誘導多能幹」(iPS) 細胞所做分析顯示,它們比在體外生成的iPS細胞更接近胚胎幹細胞。這些活體iPS細胞還具有生成表達胚胎標記和胚胎外標記的胚胎樣結構的潛力,這說明它們具有傳統iPS細胞或胚胎幹細胞所沒有的全能特徵。(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 Ca?amero,Teresa Rayon,Inmaculada Ors,Osvaldo Gra?a, 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.