Biology subjects

Brzechffa, C.

Publications and source records attributed to Brzechffa, C..

3 recordsLinked to original sources

bioRxiv2026

Clonal hematopoiesis-associated DNMT3A mutations derepress bivalent Polycomb target genes and enhance macrophage migration

Somatic mutations in the de novo DNA methyltransferase DNMT3A are frequent in clonal hematopoiesis, but how they alter the function of differentiated myeloid cells remains unclear. Here, we used isogenic human embryonic stem cell-derived macrophage models to define the consequences of DNMT3A dysfunction during myeloid differentiation. DNMT3A-mutant macrophages selectively upregulated bivalent Polycomb target genes, accompanied by DNA hypomethylation, reduced H3K27me3 and increased promoter accessibility. Despite broad epigenetic changes across bivalent promoters, transcriptional derepression occurred at a subset of loci characterized by lower baseline DNA methylation and higher H3K27me3, identifying pre-existing chromatin state as a determinant of transcriptional response. This Polycomb-associated program was conserved in murine macrophages and enriched for genes involved in cell migration and wound repair. DNMT3A-mutant macrophages exhibited enhanced migration and preferential early recruitment to injured tissue. These findings link clonal hematopoiesis-associated epigenetic alterations to selective transcriptional reprogramming and altered function of differentiated myeloid cells.

cell biology↗

bioRxiv2025

Cigarette Smoke and E-Cigarette Aerosol Extracts Induce Myelopoiesis and Suppress Inflammatory Cytokine Production

Tobacco and nicotine use remain the leading preventable drivers of cancer risk, and both direct and secondhand exposure to combustible cigarettes or electronic nicotine devices perturbs immune function and hematopoiesis. Here, we evaluate the impact of e-cigarette vapor and combustible cigarette smoke on in vitro cell inflammatory responses and in vivo long-term hematopoietic differentiation. In cell-based studies, cigarette smoke extract (CSE) and e-cigarette vapor extract (EVE) consistently suppress LPS-induced TNF- secretion across macrophage/monocyte models, including primary mouse and human cells and complementary cell lines, indicating a reproducible immunosuppressive effect on mature myeloid cells. Brief ex vivo exposure to CSE also alters myeloid subset composition and modifies the proliferative behavior of Tet2-knockout cells, suggesting that smoke-related cues can reshape competitive dynamics among mutant and wild-type myeloid progenitors. To assess consequences of smoking behavior in vivo, we used a custom nose-cone inhalation system to deliver controlled exposures to combustible cigarette smoke or e-cigarette aerosol to mice. Chronic exposure increased myeloid proliferation, consistent with smoking behavior inducing premature aging of the hematopoietic stem cell pool. Thus, these studies support a model in which tobacco exposures blunt innate immune responsiveness while simultaneously driving myeloid expansion conditions that accelerate hematopoietic aging.

cancer biology↗

bioRxiv2022

A dynamic epibiont community associated with the bone eating worm Osedax

Osedax, the deep-sea annelid found at sunken whalefalls, is known to host Oceanospirillales bacterial endosymbionts intracellularly in specialized roots, that help it feed exclusively on vertebrate bones. Past studies, however, have also made mention of external bacteria on their trunks. During a 14-year study, we reveal a dynamic, yet persistent, succession of Campylobacterales integrated into the epidermis of Osedax, that change over time as the whale carcass degrades on the sea floor. The Campylobacterales associated with seven species of Osedax, which comprise 67% of the bacterial community on the trunk, are initially dominated by the genus Arcobacter (at early time points < 24 months), the Sulfurospirillum at intermediate stages (~ 50 months), and the Sulfurimonas at later stages (>140 months) of whale carcass decomposition. Metagenome analysis of the epibiont metabolic capabilities suggests a transition from heterotrophy to autotrophy along the successional gradient, and differences in their capacity to metabolize oxygen, carbon, nitrogen, and sulfur. Compared to free living relatives, the Osedax epibionts were highly enriched in transposable elements, implicating genetic exchange on the host surface, and contained numerous secretions systems with eukaryotic-like protein domains, suggesting a long evolutionary history with these enigmatic, yet widely distributed deep-sea worms

microbiology↗