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Clonal persistence dominates homeostatic intestinal IgA responses

2 months ago
Immunoglobulin A (IgA) is the most abundantly produced antibody isotype and mediates protection and homeostatic regulation at mucosal surfaces. Steady-state IgA production is supported by multiple pathways, including chronic germinal centers in gut inductive lymphoid tissues. However, we lack a detailed understanding of how IgA responses are temporally integrated across inductive and effector sites. Here, we dissect homeostatic IgA responses from the perspective of clonal repertoires in...
Britta Simons

Attenuation of ATM signaling by ROS delays replicative senescence at physiological oxygen

2 months ago
Replicative senescence is a powerful tumor suppressor pathway that curbs proliferation of human cells when a few critically-short telomeres activate the DNA damage response (DDR). We show that ATM is the sole DDR kinase responsible for the induction and maintenance of replicative senescence and that ATM inhibition can induce normal cell divisions in senescent cells. Compared to non-physiological atmospheric (∼20%) oxygen, primary fibroblast cells grown at physiological (3%) oxygen were more...
Alexander J Stuart

Epigenome-wide association study of nuclear DNA methylation in relation to mitochondrial heteroplasmy

2 months ago
We analyze 10,986 participants (mean age 77; 63% women; 54% non-White) across seven U.S. cohorts to study the relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA methylation. We identify 597 CpGs associated with heteroplasmy burden, generally showing lower methylation. These CpGs are enriched in dynamically regulated island shores and depleted in CpG islands, indicating involvement in context-specific rather than constitutive gene regulation. In HEK293T cells, we...
Meng Lai