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Colombo et al. build a morphological spectrum of over 40,000 microglia across development and disease with a topological data analysis approach that allows mapping of new conditions along these sex-region-specific and brain-region-specific atlases.
The authors generated the largest epigenome atlas of postmortem brains with Alzheimer’s disease. They reported regulatory genomic signatures associated with AD, including variability in open chromatin regions, transcription factor networks and cis-regulatory domains.
Duffy et al. profiled mRNA translation in 73 human prenatal and adult cortex samples and identified thousands of previously unknown translation events, including small open reading frames that give rise to human-specific and/or brain-specific microproteins.
Bryois et al. mapped genetic variants regulating gene expression in eight major brain cell types. They found a large number of cell-type-specific genetic effects and leveraged their results to identify novel putative risk genes for brain disorders.
Single-cell analysis of immune cells from surgically resected human epileptic brain tissues showed heterogeneity and pro-inflammatory signaling in microglia and evidence for direct interaction of microglia with T cells.
By complementing spatial transcriptomics with high-resolution proteomics, Kaufmann et al. tracked a gradient of disease severity across the brains of patients with progressive multiple sclerosis, uncovering new therapeutic opportunities to slow disease.
The existence of adult neurogenesis in primates is controversial. Hao et al. performed single-cell RNA sequencing with immunostaining and neurosphere cultures on adult macaques and revealed robust neurogenesis in the adult macaque hippocampus.
Wang et al. present a new open resource from the UK Biobank using quantitative susceptibility mapping, a neuroimaging marker sensitive to iron and myelin. They demonstrate a broad range of phenotypic and genetic associations in 35,885 participants.
The authors reconstructed the individual projectomes of 6,357 mouse prefrontal cortical projection neurons, revealing projectome-defined neuron subtypes and organizing principles of axon projections and correspondence with transcriptomes.
This study reports structural variants (SVs) discovered using 1,760 short-read whole genomes and provides a catalog linking SVs to gene regulation by mapping cis-acting SV-xQTLs with mRNA expression, splicing, histone acetylation and protein in postmortem brain tissues.
The authors obtained transcriptomes from anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with bipolar disorder and neurotypical controls. They observed decreased expression of neuroimmune and synaptic pathways.
Using single-nuclei RNA sequencing to interrogate gene expression in peripheral nerves, Yim et al. reveal diverse glial subpopulations and identify a novel myelinating Schwann cell subtype that preferentially ensheathes motor axons and is depleted in ALS nerve samples from mouse models and patients.
Answer ALS is a resource of patient-derived iPS cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This serves as a foundation to identify distinct disease subgroups.
The authors analyzed the levels of more than 8,600 proteins across more than 1,000 brain tissues to arrive at a consensus AD brain protein co-expression network that illustrates the complexity and multiple pathological processes that occur in AD, many of which are not reflected at the RNA level.
The authors measured high-resolution fMRI activity from eight individuals who saw and memorized thousands of annotated natural images over 1 year. This massive dataset enables new paths of inquiry in cognitive neuroscience and artificial intelligence.
The authors developed AAV capsids for robust transgene expression in the brain with decreased liver targeting after non-invasive administration in mice and marmosets, enabling more targeted systemic gene delivery to the brain.
The authors profile interneuron origin and molecular diversity in the human fetal brain by single-cell RNA sequencing and in situ sequencing and reveal the logic and complexity of specification of diverse interneurons in humans.
The authors generated a cell census of mouse nucleus accumbens using single-cell RNA sequencing and multiplexed error-robust FISH. These data suggest that transcriptional and spatial diversity of neuron subtypes underlies nucleus accumbens anatomic and functional heterogeneity.
Using single-cell RNA sequencing and spatial transcriptomics, Hasel et al. uncover complex reactive astrocyte subtypes that occupy distinct areas of the brain. They find two super-responders expressing unique genes in strategic locations in the brain.
Rupprecht et al. compiled a large database of simultaneous electrophysiological and calcium recordings from the same neurons. An algorithm (termed CASCADE) trained with this ground truth enables reliable spike inference without the need to tune parameters.