High-resolution molecular atlas of a lung tumor in 3D DOI Creative Commons
Tancredi Massimo Pentimalli, Simon Schallenberg, Daniel León-Periñán

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 10, 2023

ABSTRACT Cells live and interact in three-dimensional (3D) cellular neighborhoods. However, histology spatial omics methods mostly focus on 2D tissue sections. Here we present a 3D atlas of routine clinical sample, an aggressive human lung carcinoma, by combining situ quantification 960 cancer-related genes across ∼340,000 cells with measurements tissue-mechanical components. neighborhoods subdivided the tumor microenvironment into tumor, stromal, immune multicellular niches. Interestingly, pseudotime analysis suggested that pro-invasive epithelial-to-mesenchymal transition (EMT), detected stroma-infiltrating cells, already occurred one region at surface. There, myofibroblasts macrophages specifically co-localized pre-invasive their molecular signature identified patients shorter survival. Moreover, cytotoxic T-cells did not infiltrate this niche but colocalized inhibitory dendritic regulatory T cells. Importantly, systematic scoring cell-cell interactions highlighted niche-specific signaling networks accompanying invasion escape. Compared to 2D, improved characterization niches identifying niches, capturing extension T-cell boosting interactions, including druggable checkpoints. We believe communication analyses can improve design studies investigating personalized, combination immuno-oncology therapies.

Language: Английский

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning DOI Creative Commons
Jie Luo, Müge Molbay, Ying Chen

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental deep learning pipeline comprehensively quantify the targeting nanocarriers throughout mouse body at single-cell resolution. SCP-Nano reveals tissue distribution patterns lipid nanoparticles (LNPs) after different injection routes doses as low 0.0005 mg kg-1-far below detection limits conventional imaging techniques. We demonstrate that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading proteome changes, suggesting immune activation blood vessel damage. generalizes various types nanocarriers, including liposomes, polyplexes, DNA origami adeno-associated viruses (AAVs), revealing AAV2 variant transduces adipocytes body. enables comprehensive three-dimensional mapping bodies with high sensitivity should accelerate precise safe nanocarrier-based therapeutics.

Language: Английский

Citations

1
Enablers and challenges of spatial omics, a melting pot of technologies DOI Creative Commons
Theodore Alexandrov, Julio Sáez-Rodríguez, Sinem K. Saka

et al.

Molecular Systems Biology, Journal Year: 2023, Volume and Issue: 19(11)

Published: Oct. 16, 2023

Abstract Spatial omics has emerged as a rapidly growing and fruitful field with hundreds of publications presenting novel methods for obtaining spatially resolved information any data type on spatial scales ranging from subcellular to organismal. From technology development perspective, is highly interdisciplinary that integrates imaging omics, molecular analyses, sequencing mass spectrometry, image analysis bioinformatics. The emergence this not only opened window into biology, but also created multiple opportunities, questions, challenges method developers. Here, we provide the perspective developers what makes unique. After providing brief overview state art, discuss technological enablers present our vision about future applications impact melting pot.

Language: Английский

Citations

17
HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology DOI
Jonathan Hudson, Rashida A. Ferrand, Samuel Gitau

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 134(11), P. 1546 - 1565

Published: May 23, 2024

Cardiac abnormalities were identified early in the epidemic of AIDS, predating isolation and characterization etiologic agent, HIV. Several decades later, causation pathogenesis cardiovascular disease (CVD) linked to HIV infection continue be focus intense speculation. Before widespread use antiretroviral therapy, HIV-associated CVD was primarily characterized by cardiomyopathy profound immunodeficiency. With increasing therapy use, viral load suppression, establishment immune competency, effects on system are more subtle. Yet, people living with still face an increased incidence pathology. Advances cardiac imaging modalities immunology have deepened our understanding CVD. This review provides overview integrating data from immunologic studies particular relevance population originating high-endemic regions, such as sub-Saharan Africa. The highlights key evidence gaps field suggests future directions for research better understand complex HIV-CVD interactions.

Language: Английский

Citations

7
A region‐resolved proteomic map of the human brain enabled by high‐throughput proteomics DOI Creative Commons
Johanna Tüshaus, Amirhossein Sakhteman, Severin Lechner

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(23)

Published: Nov. 2, 2023

Substantial efforts are underway to deepen our understanding of human brain morphology, structure, and function using high-resolution imaging as well high-content molecular profiling technologies. The current work adds these approaches by providing a comprehensive quantitative protein expression map 13 anatomically distinct regions covering more than 11,000 proteins. This was enabled the optimization, characterization, implementation high-sensitivity high-throughput microflow liquid chromatography timsTOF tandem mass spectrometry system (LC-MS/MS) capable analyzing 2,000 consecutive samples prepared from formalin-fixed paraffin embedded (FFPE) material. Analysis this proteomic resource highlighted region-enriched patterns functional classes, localization differences between individual markers for specific areas. To facilitate access ease further mining data scientific community, all can be explored online in purpose-built R Shiny app (https://brain-region-atlas.proteomics.ls.tum.de).

Language: Английский

Citations

14
Genetically encoded barcodes for correlative volume electron microscopy DOI Creative Commons
Felix Sigmund, Alexander Е. Berezin,

Sofia Beliakova

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(12), P. 1734 - 1745

Published: April 17, 2023

Abstract While genetically encoded reporters are common for fluorescence microscopy, equivalent multiplexable gene electron microscopy (EM) still scarce. Here, by installing a variable number of fixation-stable metal-interacting moieties in the lumen encapsulin nanocompartments different sizes, we developed suite spherically symmetric and concentric barcodes (EMcapsulins) that readable standard EM techniques. Six classes EMcapsulins could be automatically segmented differentiated. The coding capacity was further increased arranging several into distinct patterns via set rigid spacers length. Fluorescent were expressed to monitor subcellular structures light EM. Neuronal expression Drosophila mouse brains enabled automatic identification defined cells compatible with transmission EM, scanning focused ion beam expandable palette controlled EM-readable can augment anatomical images multiplexed maps.

Language: Английский

Citations

13
Integration of MRI radiomics and clinical data for preoperative prediction of vascular invasion in breast cancer: A deep learning approach DOI
Guoyuan Pan, Zejun Pan,

Wubiao Chen

et al.

Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown, P. 110339 - 110339

Published: Jan. 1, 2025

Language: Английский

Citations

0
Spatial omics strategies for investigating human carotid atherosclerotic disease DOI Creative Commons
Jiaxin Wan,

Zhi Sun,

Xueqiong Feng

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(4)

Published: March 28, 2025

Abstract Atherosclerosis is a chronic inflammatory condition of the arteries, marked by development plaques within arterial intima. The rupture unstable can lead to thrombosis, downstream vessel occlusion and serious clinical events. composition atherosclerotic complex highly heterogeneous, posing challenges for their study. current pathology histological subtype classification may fail fully encompass microscopic molecular components in tissue, disease progress various stages atherosclerosis potential mechanism plaque rupture. However, spatial mapping heterogeneity tissue enhance our understanding these lesions. Despite considerable made traditional omics field research, its status as an indispensable technology, there remain inherent limitations investigation minute molecular. In recent years, techniques have advanced significantly, enabling visualisation analysis specific that serve causal targets associated with progression. effective application both research settings represents promising area further exploration. This review focuses on advancements findings related study extracranial carotid cerebrovascular disease. Spatial facilitate detection biomarkers diagnostic significance or relevance disease, offering new methods insights into diagnosis complications.

Language: Английский

Citations

0
Recent Advancements in Subcellular Proteomics: Growing Impact of Organellar Protein Niches on the Understanding of Cell Biology DOI
Vanya Bhushan, Aleksandra Nita‐Lazar

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(8), P. 2700 - 2722

Published: March 7, 2024

The mammalian cell is a complex entity, with membrane-bound and membrane-less organelles playing vital roles in regulating cellular homeostasis. Organellar protein niches drive discrete biological processes functions, thus maintaining equilibrium. Cellular such as signaling, growth, proliferation, motility, programmed death require dynamic movements between compartments. Aberrant localization associated wide range of diseases. Therefore, analyzing the subcellular proteome can provide comprehensive overview biology. With recent advancements mass spectrometry, imaging technology, computational tools, deep machine learning algorithms, studies pertaining to their distributions are gaining momentum. These reveal changing interaction networks because "moonlighting proteins" serve discovery tool for disease network mechanisms. Consequently, this review aims repository proteomics subcontexting methods, challenges, future perspectives method developers. In summary, crucial understanding fundamental mechanisms

Language: Английский

Citations

4
Structural brain preservation: a potential bridge to future medical technologies DOI Creative Commons
Andrew McKenzie,

Ariel Zeleznikow-Johnston,

Jordan S. Sparks

et al.

Frontiers in Medical Technology, Journal Year: 2024, Volume and Issue: 6

Published: Sept. 9, 2024

When faced with the prospect of death, some people would prefer a form long-term preservation that may allow them to be restored healthy life in future, if technology ever develops point this is feasible and humane. Some believe we have capacity perform type experimental today-although it has never been proven-using contemporary methods preserve structure brain. The idea morphomolecular organization brain encodes information required for psychological properties such as personality memories. If these structures can maintained intact over time, could theoretically provide bridge access restorative technologies future. To consider hypothesis, first describe possible metrics used assess structural quality. We next explore several brain, including traditional cryonics method cryopreservation, well aldehyde-stabilized cryopreservation fluid preservation. focus in-depth on preservation, which relies aldehyde fixation induce chemical gel formation wide set biomolecules appears cost-effective method. two theoretical recovery technologies, alongside ethical legal complexities all will require prudent approach. non-negligible chance allowing successful restoration future deserves serious research efforts by scientific community.

Language: Английский

Citations

4
Spatial proteomics of single cells and organelles on tissue slides using filter-aided expansion proteomics DOI Creative Commons
Zhen Dong, Wenhao Jiang, Chunlong Wu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 30, 2024

Language: Английский

Citations

4