Publication Date:
2009-10-10
Description:
The pluripotent state, which is first established in the primitive ectoderm cells of blastocysts, is lost progressively and irreversibly during subsequent development. For example, development of post-implantation epiblast cells from primitive ectoderm involves significant transcriptional and epigenetic changes, including DNA methylation and X chromosome inactivation, 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 cells and that differ from embryonic stem (ES) cells derived from primitive ectoderm. 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863718/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863718/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bao, Siqin -- Tang, Fuchou -- Li, Xihe -- Hayashi, Katsuhiko -- Gillich, Astrid -- Lao, Kaiqin -- Surani, M Azim -- 083089/Wellcome Trust/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Oct 29;461(7268):1292-5. doi: 10.1038/nature08534.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19816418" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Biomarkers/metabolism
;
Cadherins/metabolism
;
Cells, Cultured
;
Cellular Reprogramming
;
DNA Methylation
;
Ectoderm/cytology
;
Embryo, Mammalian/cytology
;
*Embryonic Development
;
Embryonic Stem Cells/*cytology/*metabolism
;
*Epigenesis, Genetic
;
Gene Expression Profiling
;
Germ Layers/*cytology/metabolism
;
Leukemia Inhibitory Factor/metabolism
;
Mice
;
Pluripotent Stem Cells/*cytology/*metabolism
;
STAT3 Transcription Factor/metabolism
;
Y Chromosome/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
