2026-06-14T03:44:03Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/174162024-11-29T14:36:32Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Abad, María author Mosteiro, Lluc author Pantoja, Cristina author Cañamero, Marta author Rayon, Teresa author Ors, Inmaculada author Graña, Osvaldo author Megías, Diego author Dominguez, Orlando author Martinez Garcia, Maria Dolores author Manzanares, Miguel author Ortega Jimenez, Sagrario author Serrano, Manuel author 2013-10-17 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. Nature. 2013;502(7471):340-345. 10.1038/nature12586 1476-4687 Nature 24025773 http://hdl.handle.net/20.500.12105/17416 Reprogramming in vivo produces teratomas and iPS cells with totipotency features.