Decoding the tumor microenvironment with spatial technologies

Nature Immunology, Год журнала: 2023, Номер 24(12), С. 1982 - 1993

Опубликована: Ноя. 27, 2023

Язык: Английский

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Obesity-induced inflammation: connecting the periphery to the brain

Nature Metabolism, Год журнала: 2024, Номер 6(7), С. 1237 - 1252

Опубликована: Июль 12, 2024

Язык: Английский

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Piezo2 in sensory neurons regulates systemic and adipose tissue metabolism

Cell Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Mapping of individual sensory nerve axons from digits to spinal cord with the transparent embedding solvent system

Cell Research, Год журнала: 2024, Номер 34(2), С. 124 - 139

Опубликована: Янв. 3, 2024

Abstract Achieving uniform optical resolution for a large tissue sample is major challenge deep imaging. For conventional clearing methods, loss of and quality in regions inevitable due to limited transparency. Here we describe the Transparent Embedding Solvent System (TESOS) method, which combines clearing, transparent embedding, sectioning block-face We used TESOS acquire volumetric images an adult mouse whole-body sample. The method highly versatile can be combined with different microscopy systems achieve uniformly high resolution. With light sheet microscope, imaged whole body mouse, including skin, at 0.8 × 3.5 μm 3 voxel within 120 h. confocal microscope 40×/1.3 numerical aperture objective, achieved sub-micron reveal complete projection individual nerve axons central or peripheral nervous system. Furthermore, allowed first mesoscale connectome mapping sensory neuron spanning 5 cm from digits spinal cord

Язык: Английский

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Benchtop mesoSPIM: a next-generation open-source light-sheet microscope for cleared samples

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 27, 2024

Abstract In 2015, we launched the mesoSPIM initiative, an open-source project for making light-sheet microscopy of large cleared tissues more accessible. Meanwhile, demand imaging larger samples at higher speed and resolution has increased, requiring major improvements in capabilities such microscopes. Here, introduce next-generation (“Benchtop”) with a significantly increased field view, improved resolution, throughput, affordable cost, simpler assembly compared to original version. We develop optical method testing detection objectives that enables us select optimal large-sensor cameras. The achieves high spatial (1.5 µm laterally, 3.3 axially) across entire magnification up 20×, supports sample sizes ranging from sub-mm several centimeters while being compatible multiple clearing techniques. microscope serves broad range applications neuroscience, developmental biology, pathology, even physics.

Язык: Английский

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Expanding boundaries – a cell biologist's guide to expansion microscopy

Journal of Cell Science, Год журнала: 2024, Номер 137(7)

Опубликована: Апрель 1, 2024

ABSTRACT Expansion microscopy (ExM) is a revolutionary novel approach to increase resolution in light microscopy. In contrast super-resolution methods that rely on sophisticated technological advances, including instrumentation, ExM instead entirely based sample preparation. ExM, labeled target molecules fixed cells are anchored hydrogel, which then physically enlarged by osmotic swelling. The isotropic swelling of the hydrogel pulls labels apart from one another, and their relative organization can thus be resolved using conventional microscopes even if it was below diffraction limit beforehand. As additionally benefit technical enhancements achieved microscopy, reach into nanometer range with an astoundingly low degree error induced distortion during physical expansion process. Because underlying chemistry well understood technique relatively simple procedure, easily reproducible non-expert laboratories has quickly been adopted address ever-expanding spectrum problems across life sciences. this Review, we provide overview rapidly expanding new field, summarize most important insights gained so far attempt offer outlook future developments.

Язык: Английский

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A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 23, 2024

Язык: Английский

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Integrated platform for multiscale molecular imaging and phenotyping of the human brain

Science, Год журнала: 2024, Номер 384(6701)

Опубликована: Июнь 13, 2024

Understanding cellular architectures and their connectivity is essential for interrogating system function dysfunction. However, we lack technologies mapping the multiscale details of individual cells in human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, information from same brain. The includes three core elements: vibrating microtome ultraprecision slicing large-scale tissues without losing (MEGAtome), polymer hydrogel-based tissue processing technology multiplexed imaging (mELAST), computational pipeline reconstructing three-dimensional across multiple brain slabs (UNSLICE). applied this analyzing Alzheimer's disease pathology at scales demonstrating scalable neural

Язык: Английский

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Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19

Cell Host & Microbe, Год журнала: 2024, Номер 32(12), С. 2112 - 2130.e10

Опубликована: Ноя. 29, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed accumulation of spike protein in skull-meninges-brain axis human COVID-19 patients, persisting long after viral clearance. Further, biomarkers neurodegeneration were elevated cerebrospinal fluid from COVID proteomic analysis skull, meninges, brain samples revealed dysregulated inflammatory pathways neurodegeneration-associated changes. Similar distribution patterns SARS-CoV-2-infected mice. Injection alone was sufficient to induce neuroinflammation, proteome changes axis, anxiety-like behavior, exacerbated outcomes mouse models stroke traumatic injury. Vaccination reduced but did not eliminate Our findings suggest persistent at borders may contribute lasting sequelae COVID-19.

Язык: Английский

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Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response

npj Precision Oncology, Год журнала: 2024, Номер 8(1)

Опубликована: Март 22, 2024

Abstract Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, quantification using multiplex immunohistochemistry (mIHC) staining of T B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC H&E whole-slide images (WSIs) developed deep learning model for automated segmentation TLSs. The achieved Dice coefficients 0.91 on the internal test set 0.866 external validation set, along intersection over union (IoU) scores 0.819 0.787, respectively. TLS ratio, defined as segmented area total tissue area, correlated lymphocyte levels expression CXCL13 , chemokine formation, 6140 patients spanning 16 tumor types Cancer Genome Atlas (TCGA). prognostic models overall survival indicated that inclusion ratio TNM staging significantly enhanced models’ discriminative ability, outperforming traditional solely incorporated staging, 10 out 15 TCGA types. Furthermore, when applied to biopsied treatment-naïve samples, higher ratios predicted positive response across multiple cohorts, including specific therapies esophageal squamous cell carcinoma, non-small lung cancer, stomach adenocarcinoma. In conclusion, our learning-based approach offers an reproducible method quantification, highlighting potential predicting informing cancer prognosis.

Язык: Английский

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