White adipocyte dysfunction and obesity-associated pathologies in humans

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 270 - 289

Published: Dec. 12, 2023

Language: Английский

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Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues

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

Published: Dec. 8, 2023

Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, gene signatures associated with pathological features, are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance three commercial iST on serial sections from tissue microarrays (TMAs) containing 23 tumor normal types both relative technical biological performance. On matched found that 10x Xenium shows higher transcript counts per without sacrificing specificity, but all concord to orthogonal RNA-seq datasets perform resolved cell typing, albeit different false discovery rates, segmentation error frequencies, varying degrees sub-clustering downstream analyses. Taken together, our analyses provide a comprehensive benchmark guide choice method as researchers design studies precious samples this rapidly evolving field.

Language: Английский

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Antibody-drug conjugates in breast cancer: overcoming resistance and boosting immune response

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(18)

Published: Sept. 14, 2023

Antibody-drug conjugates (ADCs) have emerged as a revolutionary therapeutic class, combining the precise targeting ability of monoclonal antibodies with potent cytotoxic effects chemotherapeutics. Notably, ADCs rapidly advanced in field breast cancer treatment. This innovative approach holds promise for strengthening immune system through antibody-mediated cellular toxicity, tumor-specific immunity, and adaptive responses. However, development upfront acquired resistance poses substantial challenges maximizing effectiveness these therapeutics, necessitating deeper understanding underlying mechanisms. These mechanisms include antigen loss, derangements ADC internalization recycling, drug clearance, alterations signaling pathways payload target. To overcome resistance, ongoing research efforts are focused on urgently identifying biomarkers, integrating therapy approaches, designing novel payloads. Review provides an overview clinical ADCs, explores their unique immune-boosting function, while also highlighting complex safety that must be addressed. A continued focus how impact tumor microenvironment will help to identify new payloads can improve patient outcomes.

Language: Английский

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Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 11 - 31

Published: Aug. 21, 2024

Language: Английский

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A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(4), P. 652 - 662

Published: March 28, 2024

Abstract Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk mastectomies. From more than 800,000 cells identified 41 subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according natural history tissue. Age, parity germline mutations, known modulate developing cancer, affected homeostatic cellular state in ways. We found BRCA1 BRCA2 carriers distinct gene expression signature indicative potential exhaustion, which was validated by immunohistochemistry. This suggests immune-escape mechanisms could manifest non-cancerous tissues very early during tumor initiation. is rich resource can be used inform novel approaches for detection prevention cancer.

Language: Английский

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Spatial landscapes of cancers: insights and opportunities

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(9), P. 660 - 674

Published: July 23, 2024

Language: Английский

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Physiological premature aging of ovarian blood vessels leads to decline in fertility in middle-aged mice

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Ovarian function declines significantly as females enter middle-age, but the mechanisms underlying this decline remain unclear. Here, we utilize whole-organ imaging to observe a notable decrease in ovarian blood vessel (oBV) density and angiogenesis intensity of middle-aged mice. This leads diminished supply ovaries, resulting inadequate development maturation follicles. Utilizing genetic-modified mouse models, demonstrate that granulosa cell secreted VEGFA governs angiogenesis, physiological oBV is not attributed insufficiency. Instead, through single-cell sequencing, identify aging vascular endothelium primary factor contributing decline. Consequently, administration salidroside, natural compound functional reverse promote enhances improve fertility older females. Our findings highlight enhancing promising strategy boost study identifies key driver loss female mice demonstrates restoring with Salidroside might be approach aged

Language: Английский

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Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 6, 2025

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot immune-cold (human papillomavirus [HPV]+ve HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF CCL19 fibroblastic reticular [FRC]-like). IL-11 iCAF were spatially associated monocytes regulated in vitro through synergistic activation canonical NF-κB signalling by IL-1β TNF-α. FRC-like enriched HPV+ve tumours, CD4 T-cells B-cells tertiary lymphoid structures non-canonical via lymphotoxin. Pan-cancer analysis revealed several 'iCAF' subgroups present normal cancer tissues; IL11 found cancers from the gastrointestinal (GI) tract transcriptomically distinct iCAFs previously described pancreatic breast greater properties; fibroblasts at low frequencies all tumour types, significantly better survival patients receiving checkpoint immunotherapy. work clarifies expands current literature on CAFs, highlighting links important immunological niches.

Language: Английский

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Single‐cell and spatial transcriptomics reveal POSTN⁺ cancer‐associated fibroblasts correlated with immune suppression and tumour progression in non‐small cell lung cancer

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(12)

Published: Dec. 1, 2023

Abstract Background Cancer‐associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, influence CAF subpopulations on progression lung is still unclear, which impedes translational advances in targeting CAFs. Methods We performed single‐cell RNA sequencing (scRNA‐seq) tumour, paired tumour‐adjacent, and normal samples from 16 non‐small cell (NSCLC) patients. were analyzed after integration with published NSCLC scRNA‐seq data. SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) was applied tumour tumour‐adjacent seven patients map architecture major populations microenvironment (TME). Immunohistochemistry (IHC) multiplexed IHC (mIHC) used validate marker gene expression association CAFs immune infiltration TME. Results A subcluster myofibroblastic POSTN + significantly enriched advanced tumours presented signatures related extracellular matrix remodeling, invasion pathways suppression. Stereo‐seq mIHC demonstrated that close localization SPP1 macrophages associated exhausted phenotype lower T cells. or abundance poor prognosis NSCLC. Conclusions Our study identified a subpopulation, might associate promote formation desmoplastic participate Furthermore, we showed clinical outcomes may provide new insights treatment

Language: Английский

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Sopa: a technology-invariant pipeline for analyses of image-based spatial omics

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

Published: June 11, 2024

Abstract Spatial omics data allow in-depth analysis of tissue architectures, opening new opportunities for biological discovery. In particular, imaging techniques offer single-cell resolutions, providing essential insights into cellular organizations and dynamics. Yet, the complexity such presents analytical challenges demands substantial computing resources. Moreover, proliferation diverse spatial technologies, as Xenium, MERSCOPE, CosMX in spatial-transcriptomics, MACSima PhenoCycler multiplex imaging, hinders generality existing tools. We introduce Sopa ( https://github.com/gustaveroussy/sopa ), a technology-invariant, memory-efficient pipeline with unified visualizer all image-based omics. Built upon universal SpatialData framework, optimizes tasks like segmentation, transcript/channel aggregation, annotation, geometric/spatial analysis. Its output includes user-friendly web reports files, well comprehensive files Overall, represents significant step toward unifying analysis, enabling more understanding interactions organization systems.

Language: Английский

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