{"doi":"10.1016/j.celrep.2025.115671","title":"Proteogenomic reprogramming to a functional human blastomere-like stem cell state via a PARP-DUX4 regulatory axis","abstract":"Here, we show that conventional human pluripotent stem cells cultured with non-specific tankyrase-PARP1-inhibited conditions underwent proteogenomic reprogramming to functional blastomere-like tankyrase/PARP inhibitor-regulated naive stem cells (TIRN-SC). TIRN-SCs concurrently expressed hundreds of pioneer factors in hybrid 2C-8C-morula-ICM programs that were augmented by induced expression of DUX4. Injection of TIRN-SCs into 8C-staged murine embryos equipotently differentiated human cells to the extra-embryonic and embryonic compartments of chimeric blastocysts and fetuses. Ectopic expression of murine-E-Cadherin in TIRN-SCs further enhanced interspecific chimeric tissue targeting. TIRN-SC-derived trophoblast stem cells efficiently generated placental chimeras. Proteome-ubiquitinome analyses revealed increased TNKS and reduced PARP1 levels and an ADP-ribosylation-deficient, hyper-ubiquitinated proteome that impacted expression of both tankyrase and PARP1 substrates. ChIP-seq of NANOG-SOX2-OCT4 and PARP1 (NSOP) revealed genome-wide NSOP co-binding at DUX4-accessible enhancers of embryonic lineage factors; suggesting a DUX4-NSOP axis regulated TIRN-SC lineage plasticity. TIRN-SCs may serve as valuable models for studying the proteogenomic regulation of pre-lineage human embryogenesis. VIDEO ABSTRACT.","journal":"Cell Reports","year":2025,"id":541109,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":586347,"name":"Ariana Angarita","orcid":null,"position":1,"is_corresponding":false},{"id":393155,"name":"Tea Soon Park","orcid":"0000-0002-2519-1291","position":2,"is_corresponding":false},{"id":394226,"name":"Rebecca Evans-Moses","orcid":null,"position":3,"is_corresponding":false},{"id":394227,"name":"Justin Thomas","orcid":null,"position":4,"is_corresponding":false},{"id":1429481,"name":"Sirui Yan","orcid":null,"position":5,"is_corresponding":false},{"id":491964,"name":"Isabel Uribe","orcid":"0000-0003-4092-3398","position":6,"is_corresponding":false},{"id":1429036,"name":"Isabella Vegas","orcid":"0009-0005-2437-7130","position":7,"is_corresponding":false},{"id":1429482,"name":"Clara Kochendoerfer","orcid":null,"position":8,"is_corresponding":false},{"id":1151356,"name":"Willem Buys","orcid":"0000-0002-4482-7750","position":9,"is_corresponding":false},{"id":236295,"name":"Anthony K. L. Leung","orcid":"0000-0001-5569-4036","position":10,"is_corresponding":false},{"id":304664,"name":"Elias T. Zambidis","orcid":"0000-0001-5452-254X","position":11,"is_corresponding":false},{"id":393156,"name":"Ludovic Zimmerlin","orcid":"0000-0002-6031-0348","position":0,"is_corresponding":true}],"reference_count":168,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40338744","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}