{"doi":"10.1101/2022.12.01.518580","title":"Multiomic Profiling of Human Clonal Hematopoiesis Reveals Genotype and Cell-Specific Inflammatory Pathway Activation","abstract":"Abstract Clonal hematopoiesis (CH) is an age-associated phenomenon that increases risk for hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood 1 . Here, we profile peripheral blood gene expression in 66,968 single cells from a cohort of 17 CH patients and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutant TET2 and DNMT3A cells to non-mutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment. Additionally, patients harboring DNMT3A and TET2 CH mutations possessed a pro-inflammatory profile in CD14+ monocytes through previously unrecognized pathways such as galectin and macrophage Inhibitory Factor (MIF). We also found that T cells from CH patients, though mostly un-mutated, had decreased expression of GTPase of the immunity associated protein (GIMAP) genes, which are critical to T cell development, suggesting that CH may impair T cell function. Key points - CD14+ monocytes from clonal hematopoiesis patients stimulate inflammation through increased cytokine expression. - T cells from clonal hematopoiesis are deficient in GIMAP expression, suggesting CH may impair T cell differentiation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297815,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":581339,"name":"Pawan Bhat","orcid":"0000-0003-0520-4363","position":1,"is_corresponding":false},{"id":33663,"name":"Alyssa Parker","orcid":"0000-0002-6632-7458","position":2,"is_corresponding":false},{"id":976703,"name":"Matthew T. Jenkins","orcid":"0000-0002-4884-3926","position":3,"is_corresponding":false},{"id":860769,"name":"Caitlyn Vlasschaert","orcid":"0009-0003-8466-7602","position":4,"is_corresponding":false},{"id":986359,"name":"Jessica Ulloa","orcid":"0009-0007-4874-987X","position":5,"is_corresponding":false},{"id":870320,"name":"Joseph C. Van Amburg","orcid":"0000-0002-1410-6995","position":6,"is_corresponding":false},{"id":864263,"name":"Chad R. Potts","orcid":"0000-0003-2319-2474","position":7,"is_corresponding":false},{"id":986910,"name":"Sydney Olson","orcid":null,"position":8,"is_corresponding":false},{"id":643945,"name":"Alexander J. Silver","orcid":"0000-0001-8255-3140","position":9,"is_corresponding":false},{"id":986360,"name":"Ayesha Ahmad","orcid":"0000-0001-5360-9387","position":10,"is_corresponding":false},{"id":983165,"name":"Brian Sharber","orcid":"0009-0005-9598-8211","position":11,"is_corresponding":false},{"id":986361,"name":"Donovan Brown","orcid":"0000-0003-3820-7050","position":12,"is_corresponding":false},{"id":682889,"name":"Ningning Hu","orcid":null,"position":13,"is_corresponding":false},{"id":68690,"name":"Peter van Galen","orcid":"0000-0002-0735-1570","position":14,"is_corresponding":false},{"id":225918,"name":"Michael R. Savona","orcid":"0000-0003-3763-5504","position":15,"is_corresponding":false},{"id":27378,"name":"Alexander G. Bick","orcid":"0000-0001-5824-9595","position":16,"is_corresponding":false},{"id":392054,"name":"P. Brent Ferrell","orcid":"0000-0003-1140-9154","position":17,"is_corresponding":false},{"id":859223,"name":"J. Brett Heimlich","orcid":"0000-0003-2812-5326","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:31:31.270564Z","pmid":null,"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":[]}