Resources in 2017

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.

The hypothalamic arcuate–median eminence (Arc-ME) complex is rich with functionally distinct cell types, a fraction of which have been characterized. The authors profile 20,921 individual cells by single-cell RNA-seq, identifying 50 Arc-ME cell types and their markers, determining each's response to energy status and implicating two neuron populations in the genetic control of obesity.

Su et al. investigated the chromatin accessibility status of neurons in the adult mouse dentate gyrus at different timepoints after activation at the genome-wide level. Their study provides a potential mechanism by which neuronal activity may reshape the epigenetic landscape, thereby dynamically changing transcriptome and neuronal properties over time.