Lamprey 3D single-cell transcriptomics reveals ancestral and specialized features of the vertebrate brain

Lampreys are jawless fish that branched off from the vertebrate lineage before jawed vertebrates arose, making them valuable for tracing the evolutionary origins of the brain. Researchers built a three-dimensional molecular atlas of the lamprey brain by combining spatial transcriptomics with single-nucleus RNA sequencing, mapping 209 distinct cell clusters across 14 brain regions. Comparing this atlas with data from other vertebrates revealed that the broad spatial layout of the brain has been conserved across hundreds of millions of years, pointing to an ancient organizational blueprint. Despite this conservation, substantial lineage-specific divergence was also evident, including extensive neuronal specialization and regulatory changes linked to the spatial reorganization and functional evolution of neuronal populations. The data also suggest that a cerebellum-like structure predates the evolution of the true cerebellum seen in jawed vertebrates. The work clarifies which aspects of neural organization are constrained by deep evolutionary history and which reflect more recent innovation.

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Tracking the roots of zoonoses

Researchers are using ancient DNA recovered from animal remains to trace where and how zoonotic diseases — illnesses that jump from animals to humans — first emerged and subsequently spread. By analyzing pathogen genetic material preserved in archaeological and paleontological specimens, scientists can reconstruct the evolutionary histories of infectious diseases far more precisely than modern genomic data alone allows. This approach is revealing the deep roots of pathogens that have shaped human history, clarifying when key host-switching events occurred and how diseases changed as they adapted to new hosts. Understanding these origins matters because it can inform how we anticipate and respond to future spillover events, given that most emerging infectious diseases originate in animal reservoirs.

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Brain-wide topographic coordination of rotating waves

Researchers investigated how traveling waves of neural activity are spatially organized across the brain in awake mice, using a combination of cortex-wide imaging and electrophysiology. They discovered that waves commonly rotate in circular patterns centered on the somatosensory cortex, sweeping across somatotopic maps. Strikingly, the underlying axonal wiring in sensory cortex mirrors this circular geometry, and when researchers surgically severed these circular circuits, rotating wave activity was substantially reduced. The waves were synchronized between the two brain hemispheres and between sensory and motor cortical regions, and also coordinated with firing in subcortical structures. Wave patterns shifted with behavioral state, could be triggered by sensory stimuli, and were engaged during accurate visuomotor tasks. The findings demonstrate that rotating brain waves are not random emergent phenomena but are actively shaped by the brain's physical wiring, and they appear functionally relevant across a range of behaviors.

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CD4 ⁺ T cells impair tumor growth through IL-3 and TNF-dependent vascular damage

Conventional cancer immunotherapy relies heavily on T cells directly killing tumor cells, but this approach faces significant clinical obstacles. Researchers discovered an alternative mechanism whereby tumor antigen-specific CD4+ T cells suppress tumor growth by damaging the tumor's blood supply rather than attacking cancer cells directly. Using multiplex immunofluorescence alongside single-cell and tissue transcriptomics, they found that these T cells trigger the assembly of myeloid cell clusters around tumor blood vessels. Within these clusters, classically activated macrophages produce TNF in response to IL-3 released by the CD4+ T cells. This TNF then damages intratumoral blood vessel endothelium and disrupts blood flow, causing localized tumor cell death through ischemia. Because this pathway does not require T cells to recognize living tumor cells, it sidesteps many of the immunosuppressive mechanisms that typically blunt anti-tumor immunity, suggesting a potentially complementary strategy for cancer treatment.

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Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques

Researchers examined how aging and early life adversity (ELA) shape DNA methylation patterns across 14 tissues in 237 semi-free-ranging rhesus macaques experiencing naturally occurring hardships. While age-related methylation changes were largely tissue-specific, epigenetic clocks built for each tissue revealed that individuals tended to age at consistent rates across tissues. Different types of ELA each left their own coordinated imprint spanning multiple tissues simultaneously. Interestingly, although ELA and aging often affected the same genomic sites, their effects pointed in opposite directions — meaning ELA does not simply accelerate epigenetic aging in a straightforward way. Instead, early adversity produces a distinct cross-tissue epigenetic signature that is entangled with, but separable from, normal aging patterns. These findings clarify how environmental conditions experienced early in life may establish molecular trajectories that influence long-term health and disease risk.

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