Single-cell multiomics reveal divergent effects of DNMT3A- and TET2-mutant clonal hematopoiesis in inflammatory response.

ABSTRACT:

Abstract

DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposed epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for progression to hematologic neoplasms. Although individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated. Here, we make use of a natural inflammatory response occurring during coronavirus disease 2019 (COVID-19), to understand the association of these mutations with inflammatory morbidity (acute respiratory distress syndrome [ARDS]) and mortality. We demonstrate the age-independent, negative impact of DNMT3A mutant (DNMT3Amt) CH on COVID-19-related ARDS

SUBMITTER: Mohammed Ismail W 

PROVIDER: S-EPMC11787483 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature