Spatial atlas of the human brain vasculature reveals specialized cell ensembles.

Multimodal brain cell atlas across the adult macaque lifespan.

High-throughput single-cell omics of non-human primate brain tissue provides a powerful platform to investigate the molecular basis of brain aging. Here, we present a comprehensive transcriptomic and chromatin accessibility atlas of 2,955,873 nuclei from eight brain regions of 23 female cynomolgus macaques spanning the adult lifespan, including exceptionally old individuals. Our analyses reveal dynamic, cell-subtype- and region-specific age-related changes in core brain functions, including synaptic communication and axon myelination. We identify multicellular networks in the pons and medulla as a previously unrecognized hotspot of primate brain aging, highlighting white matter vulnerability as a central feature of aging. Integration with human brain aging and neurodegeneration datasets reveals both shared and divergent molecular mechanisms. We further define transcription factors and age-related chromatin remodeling programs linked to longevity and neurodegeneration. This spatiotemporal atlas establishes a foundational framework for understanding the cellular and regulatory architecture of primate brain aging and its links to disease.

Cerebral vasculature shapes the spatial patterning of brain metastases

Primary cancer cells that originate in diverse tissues in the body can spread to the brain through various physiological pathways and form metastatic tumors. The spatial patterning of brain metastases is highly stereotyped across individuals, but the physiological factors that confer regional vulnerability to tumor colonization are poorly understood. Here we map the brain metastases associated with primary breast cancer, lung cancer, and malignant melanoma to the multiscale organization of the brain. We analyze structural magnetic resonance imaging (MRI) data from more than 2, 300 cancer patients with approximately 10, 000 brain metastases to estimate metastatic frequency maps. We then examine whether transcriptional (microarray profiling), functional (functional MRI), and vascular (arterial spin labeling) features can predict the spatial pattern of each brain metastasis type. Our analyses highlight vascular anatomy as an integral determinant of metastatic patterning, particularly in breast and lung cancers. We find arterial border-zones as sites of elevated vulnerability to metastatic invasion. These areas, characterized by slow flow and small-caliber vessels, create a hemodynamic environment that favors the arrest and extravasation of circulating tumor cells. Together, these results provide quantitative support for the long-standing hypothesis that vascular architecture and its biomechanical properties constrain metastatic seeding in the brain. Identifying vascular topology as a key determinant of metastatic patterning suggests that systemic vascular and metabolic factors may contribute to metastatic risk.

Multiscale spatial transcriptomics resolves the cellular and molecular architecture of the human amygdala

Single-Cell Atlas of Microglia Reveals Conserved and Divergent Cell Populations in Mouse and Human Brain 2255696

Microglia are resident immune cells in the central nervous system and a heterogenous population with notable heterogeneity across development phases, regions, and disease states. While a few ‘microglia’ single cell atlases have recently emerged to profile large microglia datasets, a comprehensive, single cell/nuclei-resolution map of microglial subtypes and functional or activation states across different species remains lacking, especially one that performs an integrative secondary analysis of existing data. Here, we present a cross-species single-cell transcriptomic atlas of microglia from mouse and human brains, spanning multiple regions, sexes and ages. We use integrated analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics datasets and tackle computational challenges like batch effect and modality integration. Our dataset encompasses over 200,000 microglial cells from adult human postmortem brains and sex as well as age-matched murine counterparts. We benchmark several integration approaches using anchor-based and deep manifold alignment methods. Our secondary analysis reveals a core set of conserved microglial subtypes, including homeostatic microglia (TMEM119+, P2RY12+), interferon-responsive microglia (ISG15+, IFIT3+), and phagocytic/activated states (CD68+, APOE+, CST7+). Notably, we identify a conserved ‘lipid-associated microglia’ (LAM) state marked by high APOE, TREM2, and GPNMB expression in both species, enriched in aging and neurodegenerative conditions. Our dataset collection, which is available via a web-interactive atlas tool, provides a valuable resource for understanding microglial diversity across species and lays the foundation for translating findings from mouse models to human. These findings support the existence of evolutionarily conserved microglial programs and highlight the need for caution when extrapolating mouse microglial states to human contexts. NA Neuroimmunology (NEUR)

Altered microglial communication in brains with Alzheimer’s Disease pathology

Expanding genetic code to generate human brain organoids with both vasculature and microglia