Conventional dendritic cells type 1 are strongly enriched, quiescent and relatively tolerogenic in local inflammatory arthritis.

Introduction: Dendritic cells (DC) are crucial for initiating and shaping immune responses. So far, little is known about the functional specialization of human DC subsets in (local) inflammatory conditions. We profiled conventional (c)DC1, cDC2 and monocytes based on phenotype, transcriptome and function from a local inflammatory site, namely synovial fluid (SF) from patients suffering from a chronic inflammatory condition, Juvenile Idiopathic Arthritis (JIA) as well as patients with rheumatoid arthritis (RA).

Dissection of neuronal splicing and implications for neurodegeneration in X-linked dystonia-parkinsonism.

X-linked dystonia-parkinsonism (XDP) is a monogenic neurodegenerative disorder of the basal ganglia, which presents as a combination of hyperkinetic movements and parkinsonian features. The underlying genetic mechanism involves the insertion of a SINE-VNTR-Alu retrotransposon within the gene. Interestingly, alterations of have been involved in multiple neurological diseases.

Recently Evolved Enhancers Emerge with High Interindividual Variability and Less Frequently Associate with Disease.

Mutations in non-coding regulatory DNA such as enhancers underlie a wide variety of diseases including developmental disorders and cancer. As enhancers rapidly evolve, understanding their function and configuration in non-human disease models can have important clinical applications. Here, we analyze enhancer configurations in tissues isolated from the common marmoset, a widely used primate model for human disease.

Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients.

Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution.

Epigenomic annotation of gene regulatory alterations during evolution of the primate brain.

Although genome sequencing has identified numerous noncoding alterations between primate species, which of those are regulatory and potentially relevant to the evolution of the human brain is unclear. Here we annotated cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee genomes using chromatin immunoprecipitation followed by sequencing (ChIP-seq) in different anatomical regions of the adult brain. We found high similarity in the genomic positioning of rhesus macaque and human CREs, suggesting that the majority of these elements were already present in a common ancestor 25 million years ago.