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An extensive profile of DNA methylation in neuronal and non-neuronal cells across four brain regions is reported, showing that differential epigenetic marks are enriched for DNA variants associated with neuropsychiatric traits.
Highly dynamic miRNA networks mediate developmental transitions during human brain development. Single-cell networks were detected by combining single-cell miRNA and mRNA profiling with HITS-CLIP analyzed with bipartite and co-expression networks.
Bienkowski et al. have created a new subregional atlas of the mouse hippocampus that integrates gene expression with anatomical connectivity to reveal the multiscale organization of the hippocampus and its connections throughout the brain.
The BRAINcode consortium found that tens of thousands of transcribed noncoding elements (TNEs) from the ‘dark matter’ of our genome are active in dopamine neurons. They may be linked to schizophrenia, Parkinson’s disease, and addiction.
Poulin et al. developed intersectional genetic approaches to target dopamine neuron subtypes defined by combinatorial gene expression. They demonstrate that dopamine neuron subtypes display distinctive projection patterns to forebrain regions.
The authors surveyed gene expression across cortical development and in individuals with schizophrenia. Three-fold more risk variants influenced expression than known. Risk genes showed developmental regulation, while diagnosis changes implicated largely treatment effects.
This PsychENCODE resource presents 157 reference maps for open-chromatin-associated histone methylation and acetylation in prefrontal and anterior cingulate cortex, linking the neuronal epigenome to the genetic risk architecture of schizophrenia.
A localized set of mRNA at the synapse facilitates synapse formation and plasticity. The authors show an enrichment of N6-methyladenosine (m6A) modifications of these mRNA at the synapse and link m6A recognition by molecular readers to synaptic function.
Using single-cell RNA-seq, the authors produced a comprehensive atlas of the somatosensory spinal cord. They found that neuron types build the dorsal horn by a discrete layering and to be differentially engaged by noxious heat and cold.
The authors developed a CUBIC tissue clearing and expansion method to generate an editable, point-based single-cell-resolution brain atlas. This atlas, termed CUBIC-Atlas, can be used for unbiased systems-level cellular analysis in whole mouse brain.
Using single-cell RNA-seq, the authors show that early developmental neurogenesis in the dentate gyrus of the hippocampus is largely conserved in the adult, but with a perinatal transformation of stem cells to an adult type.
Using single-cell RNA-sequencing, the authors record snapshots of the dynamic sensory-experience-dependent transcriptome across all cell types of the visual cortex in mice exposed to a light stimulus. The authors note diverse cell-type-specific programs in pyramidal neuron subtypes and robust non-neuronal responses that may regulate experience-dependent neurovascular coupling and myelination.
The protein composition of excitatory synapses differs in the areas of the human neocortex controlling language, emotion and other behaviors. This neocortical postsynaptic proteome data resource can be used to link genetics to brain imaging and behavior.
Quantitative mass spectrometry was used to produce a proteomic survey of postnatal human brain regions. Compared to matched RNA-seq, protein levels showed more regional variation, especially for membrane-associated proteins in the neocortex.
This paper reports the availability of a new Resource with RNA-seq, DNA methylation and H3K9Ac QTL results from 411 brain samples. Many xQTL SNPs influence multiple molecular features, and the authors observe epigenetic mediation of eQTLs in some cases. Reanalyzing GWAS with an xQTL-weighted approach detected 20 new CNS disease susceptibility loci.
Korin et al. use CyTOF mass cytometry to characterize immune cell populations in the naive mouse brain (parenchyma, choroid plexus and meninges). This single-cell analysis of cell-surface proteins reveals the presence and phenotype of distinctive immune populations in the mouse brain compartment.
Microglia are the macrophages of the CNS, with innate neuroimmune function, and play important roles in tissue homeostasis, CNS development and neurodegeneration. Here human microglial gene expression profiles were generated. Human and mouse microglia were highly similar, except for aging-regulated genes, indicating that microglial aging differs between humans and mice.
Using large-scale analysis of protein interactions and bioinformatics, Li et al. describe the organization of the core-scaffold machinery of the postsynaptic density and its assembly in protein-interaction networks. The authors show how mutations associated with complex brain disorders are distributed along spatiotemporal protein complexes and modulate their protein interactions.
By sectioning and sequencing the prefrontal cortex of humans, chimpanzees and macaques, He et al. compiled comprehensive transcriptome atlases of cortical layers. The study provides scores of previously uncharacterized layer-marker genes and more than a hundred human-specific genes, implying that the human neocortex has evolved more than was previously appreciated.
Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-number loci, which account for 11% of the cases. They also found that individuals bearing mutations in ASD-risk genes had lower adaptive ability.