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The authors construct brain-wide coexpression networks to characterize regional versus global features, determine if disease susceptibility maps onto regional or brain-wide processes and assess how these networks capture genetic models of disease risk.
Yang et al. generated a genomic atlas of protein levels in brain, cerebrospinal fluid and plasma and used human genetics approaches to identify proteins implicated in neurological diseases as well as druggable targets.
This work provides a first molecular view of dendritic spines, for both the mushroom and stubby classes, obtained by integrating electron microscopy, quantitative biochemistry, super-resolution microscopy and 3D molecular visualizations.
SPLiT-seq single-nucleus RNA sequencing of the developing human cerebellum reveals cell-type complexities and prolonged maturation compared to mouse with important disease implications.
This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.
Tian et al. conducted a genome-wide CRISPRi/CRISPRa screen in human neurons and uncovered a neuron-specific link among prosaposin, lipofuscin and ferroptosis. The CRISPRbrain data commons enables comparison of gene function across human cell types.
The Elliott and Smith teams used imaging and genetics data from 40,000 volunteers in the UK Biobank healthcare study, discovering new genetic influences over brain structure and function, which are of relevance to both rare and common diseases.
Single-cell RNA-seq and CITE-seq were used to profile the glioblastoma immune landscape in humans and mice, revealing the diversity and dynamics of tumor macrophages as the disease progresses from initial diagnosis to recurrence.
Eze et al. use single-cell sequencing and immunohistochemical validation to create an atlas of early human brain development. In the telencephalon, they discover a diversity of progenitor subtypes, including two that are enriched in humans.
Blum et al. performed single-nucleus RNA sequencing of the adult mouse spinal cord. This analysis revealed heterogeneity in the autonomic and skeletal motor systems and provides a resource to study motor neurons in health and disease.
This study defined spatial gene expression in the human dorsolateral prefrontal cortex. It reveals layer-enriched expression of genes associated with schizophrenia and autism, highlighting the clinical relevance of spatially defined expression.
Boulting et al. profile activity-dependent gene expression and regulatory elements in human induced pluripotent stem cell-derived GABAergic neurons and uncover a possible role for calcium-responsive gene promoters of these neurons in autism risk.
Leng et al. uncover the molecular signature of neuronal subpopulations that are selectively vulnerable to tau aggregation and death early in Alzheimer’s disease in the human entorhinal cortex and other brain regions, validating RORB as a marker.
The authors show that a coordinated epigenetic priming event during memory encoding and consolidation facilitates promoter–enhancer interactions that are vital for the unique transcriptional output of reactivated engram neurons.
By analyzing hundreds of mice treated with a library of neuro- and psychoactive drugs, Wiltschko et al. show that Motion Sequencing can effectively discriminate and categorize drug effects and link molecular targets to behavioral syllables.
The ventral hippocampus is central in the processing of emotional information. Here, a combination of viral and sequencing approaches defines the organizational logic of the extended ventral CA1 circuit.
Chen et al. define previously unreported zebrafish astrocytes, provide new insights into vertebrate astrocyte development and lay the foundation for studying astrocyte function in the entire nervous system of an intact and behaving animal.
Single-nucleus transcriptomics reveal brain alterations associated with major depression. Deep layer excitatory cells and immature oligodendrocytes showed most changes, involving synaptic plasticity, immune function and steroid hormones.
The authors identify two subsets of peripheral nerve macrophages residing in the endoneurium and the epineurium and displaying a distinct transcriptome and response to injury. These cells lack the main microglia identity and have a distinct origin.
Wen et al. combined single-cell RNA-seq and spatiotemporal analysis techniques to characterize the basic cell types in the mouse SCN, identifying their spatial distributions and circadian and light-induced gene expression patterns.