{"doi":"10.1172/jci.insight.135204","title":"Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction","abstract":"Clonal hematopoiesis of indeterminate potential is prevalent in elderly individuals and associated with increased risks of all-cause mortality and cardiovascular disease. However, mouse models to study the dynamics of clonal hematopoiesis and its consequences on the cardiovascular system under homeostatic conditions are lacking. We developed a model of clonal hematopoiesis using adoptive transfer of unfractionated ten-eleven translocation 2-mutant (Tet2-mutant) bone marrow cells into nonirradiated mice. Consistent with age-related clonal hematopoiesis observed in humans, these mice displayed a progressive expansion of Tet2-deficient cells in multiple hematopoietic stem and progenitor cell fractions and blood cell lineages. The expansion of the Tet2-mutant fraction was also observed in bone marrow-derived CCR2+ myeloid cell populations within the heart, but there was a negligible impact on the yolk sac-derived CCR2- cardiac-resident macrophage population. Transcriptome profiling revealed an enhanced inflammatory signature in the donor-derived macrophages isolated from the heart. Mice receiving Tet2-deficient bone marrow cells spontaneously developed age-related cardiac dysfunction characterized by greater hypertrophy and fibrosis. Altogether, we show that Tet2-mediated hematopoiesis contributes to cardiac dysfunction in a nonconditioned setting that faithfully models human clonal hematopoiesis in unperturbed bone marrow. Our data support clinical findings that clonal hematopoiesis per se may contribute to diminished health span.","journal":"JCI Insight","year":2020,"id":51173,"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":165,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254777,"name":"Soichi Sano","orcid":"0000-0002-3361-0839","position":1,"is_corresponding":false},{"id":254778,"name":"Yoshimitsu Yura","orcid":"0000-0003-2618-8569","position":2,"is_corresponding":false},{"id":254779,"name":"Zhonghe Ke","orcid":"0000-0003-2350-0959","position":3,"is_corresponding":false},{"id":256967,"name":"Miho Sano","orcid":null,"position":4,"is_corresponding":false},{"id":165731,"name":"Kosei Oshima","orcid":null,"position":5,"is_corresponding":false},{"id":254780,"name":"Hayato Ogawa","orcid":"0000-0002-1313-4230","position":6,"is_corresponding":false},{"id":256968,"name":"Keita Horitani","orcid":null,"position":7,"is_corresponding":false},{"id":254781,"name":"Kyung‐Duk Min","orcid":"0000-0002-1000-2187","position":8,"is_corresponding":false},{"id":254782,"name":"Emiri Miura‐Yura","orcid":"0000-0002-5477-5886","position":9,"is_corresponding":false},{"id":256969,"name":"Anupreet Kour","orcid":null,"position":10,"is_corresponding":false},{"id":254783,"name":"Megan A. Evans","orcid":"0000-0001-7020-8753","position":11,"is_corresponding":false},{"id":245949,"name":"María A. Zuriaga","orcid":"0000-0003-0422-2965","position":12,"is_corresponding":false},{"id":254784,"name":"Karen K. Hirschi","orcid":"0000-0001-7116-0130","position":13,"is_corresponding":false},{"id":245948,"name":"José J. Fuster","orcid":"0000-0002-5970-629X","position":14,"is_corresponding":false},{"id":254785,"name":"Eric M. Pietras","orcid":"0000-0002-7339-8828","position":15,"is_corresponding":false},{"id":245959,"name":"Kenneth Walsh","orcid":"0000-0001-7580-2276","position":16,"is_corresponding":false},{"id":254776,"name":"Ying Wang","orcid":"0000-0002-6249-1859","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T20:40:28.278215Z","pmid":"32154790","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":[]}