生物
CD14型
炎症
造血
髓样
免疫学
癌症研究
细胞生物学
免疫系统
干细胞
作者
J. Brett Heimlich,Pawan Bhat,Alyssa Parker,Matthew T. Jenkins,Caitlyn Vlasschaert,Jessica Ulloa,Joseph C Van Amburg,Chad R. Potts,Sydney Olson,Alexander J. Silver,Ayesha Ahmad,Brian Sharber,Donovan Brown,Ningning Hu,Peter van Galen,Michael R. Savona,Alexander Bick,P. Brent Ferrell
出处
期刊:Blood Advances
[American Society of Hematology]
日期:2024-03-20
标识
DOI:10.1182/bloodadvances.2023011445
摘要
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 blood1. 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 impairs T cell function.
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