Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Single-cell transcriptome analyses reveal distinct gene expression signatures of severe COVID-19 in the presence of clonal hematopoiesis.


Clonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes individuals to various inflammatory responses, has been reported to be associated with COVID-19 severity. However, the immunological signature and the exact gene expression program by which the presence of CHIP exerts its clinical impact on COVID-19 remain to be elucidated. In this study, we generated a single-cell transcriptome landscape of severe COVID-19 according to the presence of CHIP using peripheral blood mononuclear cells. Patients with CHIP exhibited a potent IFN-gamma response in exacerbating inflammation, particularly in classical monocytes, compared to patients without CHIP. To dissect the regulatory mechanism of CHIP (+)-specific IFN-gamma response gene expression in severe COVID-19, we identified DNMT3A CHIP mutation-dependent differentially methylated regions (DMRs) and annotated their putative target genes based on long-range chromatin interactions. We revealed that CHIP mutant-driven hypo-DMRs at poised cis-regulatory elements appear to facilitate the CHIP (+)-specific IFN-gamma-mediated inflammatory immune response. Our results highlight that the presence of CHIP may increase the susceptibility to hyperinflammation through the reorganization of chromatin architecture, establishing a novel subgroup of severe COVID-19 patients.

Authors: Choi B, Kang CK, Park S, Lee D, Lee AJ, Ko Y, Kang SJ, Kang K, Kim S, Koh Y, Jung I,
Journal: Exp Mol Med;2022 Oct;54(10):1756-1765. doi:10.1038/s12276-022-00866-1
Year: 2022
PubMed: PMID: 36229591 (Go to PubMed)