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Spatial transcriptomics (ST) enables systematic profiling of whole-transcriptome gene expression in tissues while preserving spatial context. Recent advances in sequencing- and imaging-based ST technologies have ushered in the era of microscopic-resolution ST (μST), allowing transcriptome mapping at cellular and even subcellular scales with unprecedented precision. Despite these advances, μST faces substantial challenges, including sparse transcript discovery per submicron (or micron)-sized spatial units and data fragmentation across platforms, hindering integration and analysis. There is also a growing demand for scalable, segmentation-free, and universally applicable analysis methods, as well as strategies for 3D mapping, multi-omics integration, and artificial intelligence (AI)-driven spatial analysis. In this review, we highlight recent breakthroughs, outline key challenges, and discuss emerging experimental and computational solutions shaping the future of μST.
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http://dx.doi.org/10.1016/j.tig.2025.05.002 | DOI Listing |
ACS Chem Neurosci
September 2025
Chemical and Biomolecular Engineering Dept, University of California, Los Angeles, Los Angeles, California 90095, United States.
Simulations in three dimensions and time provide guidance on implantable, electroenzymatic glutamate sensor design; relative placement in planar sensor arrays; feasibility of sensing synaptic release events; and interpretation of sensor data. Electroenzymatic sensors based on the immobilization of oxidases on microelectrodes have proven valuable for the monitoring of neurotransmitter signaling in deep brain structures; however, the complex extracellular milieu featuring slow diffusive mass transport makes rational sensor design and data interpretation challenging. Simulations show that miniaturization of the disk-shaped device size below a radius of ∼25 μm improves sensitivity, spatial resolution, and the accuracy of glutamate concentration measurements based on calibration factors determined .
View Article and Find Full Text PDFJ Phys Chem B
September 2025
Hefei National Research Center for Physical Sciences at the Microscale and Key Laboratory of Precision and Intelligent Chemistry, Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.
Multivalent protein-protein interactions play essential roles in mediating liquid-liquid phase separation (LLPS) that drives biomolecular condensate formation. Here, we systematically investigate how the spatial distribution and relative size of protein binding domains (PBDs) would influence LLPS in a mixture of spherical proteins and RNA single strands by using a patchy-particle polymer model, wherein each protein contains a fixed number of PBDs on the surface distributed closely or sparsely. Intriguingly, we find that LLPS behavior exhibits a nontrivial dependence on the cooperative interplay between PBD distribution and protein size: while sparsely distributed PBDs are more favorable to LLPS for small proteins, closely packed PBDs facilitate LLPS for larger counterparts.
View Article and Find Full Text PDFFish Physiol Biochem
September 2025
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Mumbai, 56, India.
Zebrafish models have been used to research Alzheimer's disease and other neurodegenerative disorders because of their similarities to the human genetic composition and behavior. Researchers have detected iron accumulation in the post-mortem brain sections of neurodegenerative disorder patients. Therefore, the development an animal model to simulate these clinical pathological findings is important.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu P. R. China.
Advances in molecular analysis and characterization techniques should revolutionize the methods for scientific exploration across physics, chemistry, and biology, fundamentally overturning our understanding of interactions and processes that govern molecular behavior at the microscopic level. Currently, the absence of a molecular analysis method that can both quantify molecules and achieve single-molecule spatial resolution hinders our study of complex molecular systems in sorption and catalysis. Here, we propose a quantitative analysis strategy for small molecules confined in ZSM-5, a zeolite material extensively used in catalysis and gas separation, based on low-dose transmission electron microscopy.
View Article and Find Full Text PDFCancer Discov
September 2025
Evolutionary Dynamics Group, Centre for Cancer Evolution, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Unlabelled: Oncogenes amplified on extrachromosomal DNA (ecDNA) contribute to treatment resistance and poor survival across cancers. Currently, the spatiotemporal evolution of ecDNA remains poorly understood. In this study, we integrate computational modeling with samples from 94 treatment-naive human glioblastomas (GBM) to investigate the spatiotemporal evolution of ecDNA.
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