{"doi":"10.1101/2025.08.29.673172","title":"A thymus-independent artificial organoid system supports complete thymopoiesis from Rhesus macaque-derived hematopoietic stem and progenitor cells","abstract":"Abstract Thymic output has been extensively studied. While advanced ex-vivo T cell generative approaches exist for mouse and human models, such advancements for nonhuman primate model are lacking. We report the establishment of a rhesus macaque-specific artificial thymic organoid (Rh-ATO) system enabling robust ex vivo T cell generation from CD34⁺ hematopoietic stem and progenitor cells (HSPCs). A continuum of distinct thymopoietic stages were recorded - robust T cell specification of HSPCs resembling thymus seeding progenitors, emergence of CD4+CD3-immature single positive, CD4+CD8+ double positive thymocytes, and finally, generation of CD4⁺ and CD8⁺ single-positive T cell subsets expressing CD38, consistent with recent thymic emigrant phenotype. These events closely mirrored Bonafide thymopoietic stages observed in the thymus. T cells expressed TCRs and exhibited polyfunctional cytokine expression. Thus, we report first demonstration of an off the shelf NHP-specific 3D system recapitulating thymopoiesis, providing a translational platform for modeling T cell development, therapeutic strategies, and immunopathogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558985,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"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":1460213,"name":"Saleem Anwar","orcid":null,"position":1,"is_corresponding":false},{"id":1460214,"name":"Yu-Tim Yau","orcid":null,"position":2,"is_corresponding":false},{"id":109017,"name":"Sunil Badve","orcid":"0000-0001-8861-9980","position":3,"is_corresponding":false},{"id":1460215,"name":"Yesim Gokmen Polar","orcid":null,"position":4,"is_corresponding":false},{"id":226173,"name":"John D. Roback","orcid":"0000-0001-9952-2252","position":5,"is_corresponding":false},{"id":253824,"name":"Rama Rao Amara","orcid":"0000-0002-6309-6797","position":6,"is_corresponding":false},{"id":551177,"name":"R. Paul Johnson","orcid":null,"position":7,"is_corresponding":false},{"id":424700,"name":"Sheikh Abdul Rahman","orcid":"0000-0002-3832-2713","position":8,"is_corresponding":false},{"id":1460212,"name":"Callie Wilde","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40949954","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":[]}