Transient naive reprogramming corrects hiPS cells functionally and epigenetically.

Autor: Buckberry S; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.; Telethon Kids Institute, Perth, Western Australia, Australia.; John Curtin School of Medical Research, College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Australia., Liu X; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.; School of Life Sciences, Westlake University, Hangzhou, China.; Research Center for Industries of the Future, Westlake University, Hangzhou, China.; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.; Westlake Institute for Advanced Study, Hangzhou, China., Poppe D; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia., Tan JP; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia., Sun G; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia., Chen J; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia., Nguyen TV; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia., de Mendoza A; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia.; School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK., Pflueger J; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia., Frazer T; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia., Vargas-Landín DB; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia., Paynter JM; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia., Smits N; Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia., Liu N; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., Ouyang JF; Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, Singapore., Rossello FJ; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.; Murdoch Children's Research Institute, Melbourne, Victoria, Australia., Chy HS; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Melbourne, Victoria, Australia., Rackham OJL; Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, Singapore.; School of Biological Sciences, University of Southampton, Southampton, UK., Laslett AL; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.; Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Melbourne, Victoria, Australia., Breen J; John Curtin School of Medical Research, College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Australia.; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., Faulkner GJ; Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Nefzger CM; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia.; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Polo JM; Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia. jose.polo@monash.edu.; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Melbourne, Victoria, Australia. jose.polo@monash.edu.; Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia. jose.polo@monash.edu.; Adelaide Centre for Epigenetics, School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia. jose.polo@monash.edu.; The South Australian Immunogenomics Cancer Institute, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia. jose.polo@monash.edu., Lister R; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia. ryan.lister@uwa.edu.au.; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, Western Australia, Australia. ryan.lister@uwa.edu.au.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Aug; Vol. 620 (7975), pp. 863-872. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1038/s41586-023-06424-7
Abstrakt: Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function 1-8 . These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory.
(© 2023. The Author(s).)
Databáze: MEDLINE
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