Suppression of induced pluripotent stem cell generation by the p53–p21 pathway Export

@article{citeulike:5403461, abstract = {Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10\% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.}, author = {Hong, Hyenjong and Takahashi, Kazutoshi and Ichisaka, Tomoko and Aoi, Takashi and Kanagawa, Osami and Nakagawa, Masato and Okita, Keisuke and Yamanaka, Shinya}, citeulike-article-id = {5403461}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature08235}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature08235}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19668191}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19668191}, day = {27}, doi = {10.1038/nature08235}, issn = {1476-4687}, journal = {Nature}, keywords = {stemcells}, month = {August}, number = {7259}, pages = {1132--1135}, posted-at = {2009-08-28 14:56:18}, priority = {2}, publisher = {Macmillan Publishers Limited. All rights reserved}, title = {Suppression of induced pluripotent stem cell generation by the p53–p21 pathway}, url = {http://dx.doi.org/10.1038/nature08235}, volume = {460}, year = {2009} }

TY - JOUR ID - citeulike:5403461 L3 - citeulike-article-id:5403461 N2 - Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation. IS - 7259 JF - Nature SN - 1476-4687 EP - 1135 TI - Suppression of induced pluripotent stem cell generation by the p53–p21 pathway PB - Macmillan Publishers Limited. All rights reserved VL - 460 SP - 1132 KW - stemcells AU - Hong, Hyenjong AU - Takahashi, Kazutoshi AU - Ichisaka, Tomoko AU - Aoi, Takashi AU - Kanagawa, Osami AU - Nakagawa, Masato AU - Okita, Keisuke AU - Yamanaka, Shinya PY - 2009/08/27/ UR - http://dx.doi.org/10.1038/nature08235 ER -