Biology subjects

Were, F.

Publications and source records attributed to Were, F..

3 recordsLinked to original sources

bioRxiv2026

An enhancer-centric approach applied to human immune system epigenomes revealed the association of macrophage enhancers with cardiovascular disease

Complex diseases are influenced by both genetic and environmental factors. Immune cells are key mediating interactions with the environment, but the impact of genetic variation on the immune system and how it influences complex diseases is not fully understood. Moreover, most genome-wide analyses (GWAS) variants associated with complex diseases are non-coding and difficult to interpret. Here, we investigated the association of non-coding variants with immune cell enhancers. As part of BLUEPRINT and the International Human Epigenome (IHEC) consortia, we generated and analysed a comprehensive set of epigenomes for human primary immune cells, including 107 epigenomes derived from 749 ChIP-Seq experiments across 24 cell types. We identified multicell enhancer activity patterns across the genome and examined their links with non-coding variants from 518 GWAS traits. This analysis revealed 117 significant associations, including novel links between cardiovascular disease variants and macrophage-specific enhancers that regulate genes involved in lipid metabolism and immunity, such as the gene encoding for the nuclear receptor LXR-alpha (NR1H3) and many of its known target genes. Together, these data will help to better understand the influence of genetic variability in immune function and related diseases.

genomics↗

bioRxiv2018

Epigenomic and functional dynamics of human bone marrow myeloid differentiation to mature blood neutrophils

Neutrophils are short-lived blood cells that play a critical role in host defense against infections. To better comprehend neutrophil functions and their regulation, we provide a complete epigenetic and functional overview of their differentiation stages from bone marrow-residing progenitors to mature circulating cells. Integration of epigenetic and transcriptome dynamics reveals an enforced regulation of differentiation, through cellular functions such as: release of proteases, respiratory burst, cell cycle regulation and apoptosis. We observe an early establishment of the cytotoxic capability, whilst the signaling components that activate antimicrobial mechanisms are transcribed at later stages, outside the bone marrow, thus preventing toxic effects in the bone marrow niche. Altogether, these data reveal how the developmental dynamics of the epigenetic landscape orchestrate the daily production of large number of neutrophils required for innate host defense and provide a comprehensive overview of the epigenomes of differentiating human neutrophils.\n\nKey pointsO_LIDynamic acetylation enforces human neutrophil progenitor differentiation.\nC_LI\n\nO_LINeutrophils cytotoxic capability is established early at the (pro)myelocyte stage.\nC_LI\n\nO_LICoordinated signaling component expression prevents unwanted toxic effects to the bone marrow niche.\nC_LI

immunology↗

bioRxiv2016

Searching for the chromatin determinants of human hematopoiesis

Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify forty-two human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis. The analysis of the orthogonal dimension of the chromatin space identify 32,662 chromatin determinant regions (CDRs), genomic regions with different epigenetic characteristics between the cell types. Functional analysis revealed that these regions are linked with cell identities. The inclusion of leukemia epigenomes in the healthy hematological chromatin sample space gives us insights on the healthy cell types that are more epigenetically similar to the disease samples. Further analysis of tumoral epigenetic alterations in hematopoietic CDRs points to sets of genes that are tightly regulated in leukemic transformations and commonly mutated in other tumors. Our method provides an analytical approach to study the relationship between epigenomic changes and cell lineage differentiation. Method availability: https://github.com/david-juan/ChromDet

genomics↗