{"ID": "PMID:37587336", "lab": {"@type": ["Lab", "Item"], "uuid": "d3412190-317a-4837-823f-3892b9f641a4", "display_title": "External Lab", "status": "current", "title": "External Lab", "@id": "/labs/external-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.d3412190-317a-4837-823f-3892b9f641a4"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/37587336", "tags": ["4dn-external-reuse"], "award": {"project": "External", "center_title": "External", "@type": ["Award", "Item"], "display_title": "EXTERNAL AWARD", "center": "External", "uuid": "12a92962-8265-4fc0-b2f8-cf14f05db58b", "@id": "/awards/external-award/", "status": "current", "name": "external-award", "description": "Funding source is from outside 4DN.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Transient naive reprogramming corrects hiPS cells functionally and  epigenetically.", "status": "current", "aliases": ["4dn-dcic-lab:PMID:37587336"], "authors": ["Buckberry S", "Liu X", "Poppe D", "Tan JP", "Sun G", "Chen J", "Nguyen TV", "de Mendoza A", "Pflueger J", "Frazer T", "Vargas-Landin DB", "Paynter JM", "Smits N", "Liu N", "Ouyang JF", "Rossello FJ", "Chy HS", "Rackham OJL", "Laslett AL", "Breen J", "Faulkner GJ", "Nefzger CM", "Polo JM", "Lister R"], "journal": "Nature", "abstract": "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.", "date_created": "2024-02-13T21:58:33.834763+00:00", "published_by": "External", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-03-15T16:02:11.250307+00:00"}, "date_published": "2023-08", "public_release": "2024-03-15", "schema_version": "2", "project_release": "2024-03-15", "exp_sets_used_in_pub": [{"uuid": "a6b5bf0d-1ee3-4f3b-b8c8-75fd834b083e", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "display_title": "4DNESXZ4FW4T", "@id": "/experiment-set-replicates/4DNESXZ4FW4T/", "status": "released", "experimentset_type": "replicate", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@id": "/publications/0d4af084-38e2-4a91-aa63-b170ffbe252b/", "@type": ["Publication", "Item"], "uuid": "0d4af084-38e2-4a91-aa63-b170ffbe252b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Buckberry S et al. (2023) PMID:37587336", "external_references": [], "short_attribution": "Buckberry S et al. (2023)", "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}