Guo, G. orcid.org/0000-0002-3273-9147, von Meyenn, F., Rostovskaya, M. et al. (9 more authors) (2017) Epigenetic resetting of human pluripotency. Development, 144 (15). pp. 2748-2763. ISSN 0950-1991
Abstract
Much attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide a method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset cells can be expanded without feeders with a doubling time of around 24 h. WNT inhibition stabilises the resetting process. The transcriptome of reset cells diverges markedly from that of primed PSCs and shares features with human inner cell mass (ICM). Reset cells activate expression of primate-specific transposable elements. DNA methylation is globally reduced to a level equivalent to that in the ICM and is non-random, with gain of methylation at specific loci. Methylation imprints are mostly lost, however. Reset cells can be re-primed to undergo tri-lineage differentiation and germline specification. In female reset cells, appearance of biallelic X-linked gene transcription indicates reactivation of the silenced X chromosome. On reconversion to primed status, XIST-induced silencing restores monoallelic gene expression. The facile and robust conversion routine with accompanying data resources will enable widespread utilisation, interrogation, and refinement of candidate naïve cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Differentiation; Human embryo; Methylome; Pluripotent stem cells; Reprogramming; Animals; Cell Differentiation; Cell Line; DNA Methylation; DNA Transposable Elements; Embryo, Mammalian; Embryonic Stem Cells; Epigenesis, Genetic; Flow Cytometry; Genes, X-Linked; Humans; In Situ Hybridization, Fluorescence; Mice; Pluripotent Stem Cells; Real-Time Polymerase Chain Reaction; X Chromosome Inactivation |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Jun 2024 14:40 |
Last Modified: | 01 Jul 2024 08:56 |
Status: | Published |
Publisher: | The Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/dev.146811 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:213059 |