-
Article
Open AccessAn expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo
Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery....
-
Article
Open AccessEpigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults
Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We...
-
Article
Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia
Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chem...
-
Article
Open AccessGenetic perturbation of PU.1 binding and chromatin loo** at neutrophil enhancers associates with autoimmune disease
Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we ...
-
Article
Open AccessIncreased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins
Rheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as al...
-
Article
Open AccessGenome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types
A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability.
-
Article
Open AccessIncreased DNA methylation variability in type 1 diabetes across three immune effector cell types
The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epige...
-
Article
Whole-genome fingerprint of the DNA methylome during human B cell differentiation
José Martín-Subero and colleagues report the whole-genome bisulfite sequencing of ten blood cell subpopulations representing the cellular stages during B cell differentiation. They find that early stages are c...
-
Article
Open AccessHigher gene expression variability in the more aggressive subtype of chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) presents two subtypes which have drastically different clinical outcomes, IgVH mutated (M-CLL) and IgVH unmutated (U-CLL). So far, these two subtypes are not associated to cl...
-
Article
Open AccessThe synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells
Glucocorticoids (GCs) cause apoptosis in malignant cells of lymphoid lineage by transcriptionally regulating a plethora of genes. As a result, GCs are included in almost all treatment protocols for lymphoid ma...
-
Article
Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia
José Martin-Subero and colleagues report whole-genome bisulfite sequencing and methylome analysis of two CLLs and three B-cell subpopulations using high-density microarrays on 139 CLLs. They identify widesprea...
