Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells Export

@article{citeulike:5951315, abstract = {The pluripotent state, which is first established in the primitive ectoderm cells of blastocysts, is lost progressively and irreversibly during subsequent development1. For example, development of post-implantation epiblast cells from primitive ectoderm involves significant transcriptional and epigenetic changes, including DNA methylation and X chromosome inactivation2, which create a robust epigenetic barrier and prevent their reversion to a primitive-ectoderm-like state. Epiblast cells are refractory to leukaemia inhibitory factor (LIF)–STAT3 signalling, but they respond to activin/basic fibroblast growth factor to form self-renewing epiblast stem cells (EpiSCs), which exhibit essential properties of epiblast cells3, 4 and that differ from embryonic stem (ES) cells derived from primitive ectoderm5. Here we show reprogramming of advanced epiblast cells from embryonic day 5.5–7.5 mouse embryos with uniform expression of N-cadherin and inactive X chromosome to ES-cell-like cells (rESCs) in response to LIF–STAT3 signalling. Cultured epiblast cells overcome the epigenetic barrier progressively as they proceed with the erasure of key properties of epiblast cells, resulting in DNA demethylation, X reactivation and expression of E-cadherin. The accompanying changes in the transcriptome result in a loss of phenotypic and epigenetic memory of epiblast cells. Using this approach, we report reversion of established EpiSCs to rESCs. Moreover, unlike epiblast and EpiSCs, rESCs contribute to somatic tissues and germ cells in chimaeras. Further studies may reveal how signalling-induced epigenetic reprogramming may promote reacquisition of pluripotency.}, author = {Bao, Siqin and Tang, Fuchou and Li, Xihe and Hayashi, Katsuhiko and Gillich, Astrid and Lao, Kaiqin and Surani, M. Azim}, citeulike-article-id = {5951315}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature08534}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature08534}, day = {08}, doi = {10.1038/nature08534}, issn = {0028-0836}, journal = {Nature}, keywords = {stemcells}, month = {October}, number = {7268}, pages = {1292--1295}, posted-at = {2009-10-30 14:49:29}, priority = {2}, publisher = {Nature Publishing Group}, title = {Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells }, url = {http://dx.doi.org/10.1038/nature08534}, volume = {461}, year = {2009} }

TY - JOUR ID - citeulike:5951315 L3 - citeulike-article-id:5951315 N2 - The pluripotent state, which is first established in the primitive ectoderm cells of blastocysts, is lost progressively and irreversibly during subsequent development1. For example, development of post-implantation epiblast cells from primitive ectoderm involves significant transcriptional and epigenetic changes, including DNA methylation and X chromosome inactivation2, which create a robust epigenetic barrier and prevent their reversion to a primitive-ectoderm-like state. Epiblast cells are refractory to leukaemia inhibitory factor (LIF)–STAT3 signalling, but they respond to activin/basic fibroblast growth factor to form self-renewing epiblast stem cells (EpiSCs), which exhibit essential properties of epiblast cells3, 4 and that differ from embryonic stem (ES) cells derived from primitive ectoderm5. Here we show reprogramming of advanced epiblast cells from embryonic day 5.5–7.5 mouse embryos with uniform expression of N-cadherin and inactive X chromosome to ES-cell-like cells (rESCs) in response to LIF–STAT3 signalling. Cultured epiblast cells overcome the epigenetic barrier progressively as they proceed with the erasure of key properties of epiblast cells, resulting in DNA demethylation, X reactivation and expression of E-cadherin. The accompanying changes in the transcriptome result in a loss of phenotypic and epigenetic memory of epiblast cells. Using this approach, we report reversion of established EpiSCs to rESCs. Moreover, unlike epiblast and EpiSCs, rESCs contribute to somatic tissues and germ cells in chimaeras. Further studies may reveal how signalling-induced epigenetic reprogramming may promote reacquisition of pluripotency. IS - 7268 JF - Nature SN - 0028-0836 EP - 1295 TI - Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells PB - Nature Publishing Group VL - 461 SP - 1292 KW - stemcells AU - Bao, Siqin AU - Tang, Fuchou AU - Li, Xihe AU - Hayashi, Katsuhiko AU - Gillich, Astrid AU - Lao, Kaiqin AU - Surani, Azim PY - 2009/10/08/ UR - http://dx.doi.org/10.1038/nature08534 ER -