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

Siqin Bao, Fuchou Tang, Xihe Li, Katsuhiko Hayashi, Astrid Gillich, Kaiqin Lao, M. Azim Surani

Research output: Contribution to journalArticle

277 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1292-1295
Number of pages4
JournalNature
Volume461
Issue number7268
DOIs
Publication statusPublished - Oct 29 2009

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Germ Layers
Pluripotent Stem Cells
Embryonic Stem Cells
Epigenomics
Ectoderm
Leukemia Inhibitory Factor
Stem Cells
Cadherins
X Chromosome Inactivation
Activins
X Chromosome
Blastocyst
Fibroblast Growth Factor 2
DNA Methylation
Transcriptome
Germ Cells
Cultured Cells
Embryonic Structures

All Science Journal Classification (ASJC) codes

  • General

Cite this

Bao, S., Tang, F., Li, X., Hayashi, K., Gillich, A., Lao, K., & Surani, M. A. (2009). Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature, 461(7268), 1292-1295. https://doi.org/10.1038/nature08534

Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. / Bao, Siqin; Tang, Fuchou; Li, Xihe; Hayashi, Katsuhiko; Gillich, Astrid; Lao, Kaiqin; Surani, M. Azim.

In: Nature, Vol. 461, No. 7268, 29.10.2009, p. 1292-1295.

Research output: Contribution to journalArticle

Bao, S, Tang, F, Li, X, Hayashi, K, Gillich, A, Lao, K & Surani, MA 2009, 'Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells', Nature, vol. 461, no. 7268, pp. 1292-1295. https://doi.org/10.1038/nature08534
Bao, Siqin ; Tang, Fuchou ; Li, Xihe ; Hayashi, Katsuhiko ; Gillich, Astrid ; Lao, Kaiqin ; Surani, M. Azim. / Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. In: Nature. 2009 ; Vol. 461, No. 7268. pp. 1292-1295.
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