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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Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(5), P. 101550 - 101550

Published: May 1, 2024

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches predict the remain elusive. Here, human cervical cancer tissues before concurrent (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8

Language: Английский

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A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation

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

Published: Jan. 2, 2025

Language: Английский

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Large-scale bulk and single-cell RNA sequencing combined with machine learning reveals glioblastoma-associated neutrophil heterogeneity and establishes a VEGFA+ neutrophil prognostic model

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: April 5, 2025

Neutrophils play a key role in the tumor microenvironment (TME); however, their functions glioblastoma (GBM) are overlooked and insufficiently studied. A detailed analysis of GBM-associated neutrophil (GBMAN) subpopulations may offer new insights opportunities for GBM immunotherapy. We analyzed single-cell RNA sequencing (scRNA-seq) data from 127 isocitrate dehydrogenase (IDH) wild-type samples to characterize GBMAN subgroups, emphasizing developmental trajectories, cellular communication, transcriptional networks. implemented 117 machine learning combinations develop novel risk model compared its performance existing glioma models. Furthermore, we assessed biological molecular features subgroups patients. From integrated large-scale scRNA-seq (498,747 cells), identified 5,032 neutrophils classified them into four distinct subtypes. VEGFA+GBMAN exhibited reduced inflammatory response characteristics tendency interact with stromal cells. these significant differences regulation. also developed termed "VEGFA+neutrophil-related signature" (VNRS) using methods. The VNRS showed higher accuracy than previously published models was an independent prognostic factor. Additionally, observed immunotherapy responses, TME interactions, chemotherapy efficacy between high-risk low-risk score groups. Our study highlights critical GBM, allowing better understanding composition GBMAN. serves as effective tool evaluating guiding clinical treatment strategies GBM. Not applicable.

Language: Английский

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Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract MAPK pathway inhibitors (MAPKi) are increasingly used in the treatment of advanced colorectal cancer, but often produce short-lived responses patients. Although acquired resistance by de novo mutations tumors have been found to reduce response some patients, additional mechanisms underlying limited durability targeting therapy remain unknown. Here, we denote new contributory tumor biology and provide insight on impact plasticity response. Analysis MAPKi treated patients revealed activation stemness programs increased ASCL2 expression, which associated with poor outcomes. Greater was also seen patient-derived CRC models, independent driver mutations. We find denotes a distinct cell population, arising from phenotypic plasticity, proliferative, stem-like phenotype, decreased sensitivity therapy, were named adaptive (APT) cells. suppression induces APT phenotype cells, resulting enrichment limiting preclinical clinical data. depletion improved efficacy extended mice. These findings uncover cellular program that mitigates therapies highlights importance addressing improve

Language: Английский

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Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract The activation and infiltration of immune cells are hallmarks ischemic stroke. However, the precise origins molecular alterations these infiltrating post‐stroke remain poorly characterized. Here, a murine model stroke (permanent middle cerebral artery occlusion [p‐MCAO]) is utilized to profile single‐cell transcriptomes in brain their potential origins, including calvarial bone marrow (CBM), femur (FBM), peripheral blood mononuclear (PBMCs). This analysis reveals transcriptomically distinct populations myeloid brain‐resident after These include novel CD14 + neutrophil subpopulation that resembles CBM neutrophils. Moreover, sequential transcription factor regulatory networks neutrophils during progression delineated, many which unique population underlie acquisition chemotaxis granule release capacities. Two disease‐related cell subtypes also identified: disease inflammatory macrophages, likely deriving from circulating monocytes skull, transcriptionally immature disease‐associated microglia, possibly arising pre‐existing homeostatic microglia. Together, comprehensive survey responses performed, encompassing both local distant sites blood.

Language: Английский

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Lineage plasticity of the integrated stress response is a hallmark of cancer evolution.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

The link between the "stress phenotype"-a well-established hallmark of cancer-and its role in tumor progression and intratumor heterogeneity remains poorly defined. integrated stress response (ISR) is a key adaptive pathway that enables survival under oncogenic stress. While ISR has been implicated promoting growth, precise driving evolution not elucidated. In this study, using genetically engineered mouse models, we demonstrate activation-indicated by elevated levels phosphorylated eIF2 (p-eIF2) ATF4-is essential for emergence dedifferentiated, therapy-resistant cell states. ISR, through coordinated actions ATF4 MYC, facilitates development populations characterized high plasticity, stemness, an epithelial-mesenchymal transition (EMT)-prone phenotype. This process driven ISR-mediated expression genes maintain mitochondrial integrity function, critical sustaining progression. Importantly, genetic, or pharmacological inhibition p-eIF2-ATF4 signaling axis leads to dysfunction significantly impairs growth models lung adenocarcinoma (LUAD). Moreover, ISR-driven dedifferentiation associated with poor prognosis therapy resistance advanced human LUAD, underscoring as promising therapeutic strategy disrupt counteract disease

Language: Английский

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Towards the Next Generation of Data‐Driven Therapeutics Using Spatially Resolved Single‐Cell Technologies and Generative AI

European Journal of Immunology, Journal Year: 2025, Volume and Issue: 55(2)

Published: Feb. 1, 2025

ABSTRACT Recent advances in multi‐omics and spatially resolved single‐cell technologies have revolutionised our ability to profile millions of cellular states, offering unprecedented opportunities understand the complex molecular landscapes human tissues both health disease. These developments hold immense potential for precision medicine, particularly rational design novel therapeutics treating inflammatory autoimmune diseases. However, vast, high‐dimensional data generated by these present significant analytical challenges, such as distinguishing technical variation from biological or defining relevant questions that leverage added spatial dimension improve understanding tissue organisation. Generative artificial intelligence (AI), specifically variational autoencoder‐ transformer‐based latent variable models, provides a powerful flexible approach addressing challenges. models make inferences about cell's intrinsic state effectively identifying patterns, reducing dimensionality modelling variability datasets. This review explores current landscape technologies, application generative AI analysis their transformative impact on By combining with advanced methodologies, we highlight insights into pathogenesis disorders outline future directions leveraging achieve goal AI‐powered personalised medicine.

Language: Английский

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A highly resolved integrated single-cell atlas of HPV-negative head and neck cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Head and Neck Squamous Cell Carcinomas (HNSCC) are the seventh most prevalent form of cancer associated with human papilloma virus infection (HPV-positive) or tobacco alcohol use (HPV-negative). HPV-negative HNSCCs have a high recurrence rate, individual patients’ responses to treatment vary greatly due level cellular heterogeneity tumor its microenvironment. Here, we describe HNSCC single cell atlas, which created by integrating six publicly available datasets encompassing over 230,000 cells across 54 patients. We contextualized relationships between existing signatures populations, identified new subpopulations, show power this large-scale resource robustly identify associations transcriptional clinical phenotypes that would not be possible discover using fewer reveal previously undefined myeloid population, sex-associated changes in type proportions, novel interactions CXCL8-positive fibroblasts vascular endothelial cells. Beyond our findings, atlas will serve as public for high-resolution characterization HNSCC.

Language: Английский

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Single‐cell transcriptional profiling reveals cellular senescence and inflammatory persistence as key features of type 1 diabetes partial remission

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

To investigate the underlying immune mechanisms during partial remission (PR) in type 1 diabetes (T1D) using single-cell RNA sequencing of peripheral blood mononuclear cells from healthy controls, newly diagnosed T1D patients, and those PR stage. We performed integrated analysis combining differential expression analysis, trajectory inference, cellular senescence evaluation transcriptional network reconstruction to characterize monocyte heterogeneity dynamic changes disease progression. identified five distinct subsets with unique molecular signatures demonstrated their stage-specific alterations. The stage was characterized by persistent inflammatory responses, evidenced expansion IL1B+ monocytes sustained activation TNF IL6-STAT3 signalling pathways, while HDAC9+ populations showed significant reduction. Notably, exhibited marked accumulation senescent across subsets, elevated senescence-associated secretory phenotype scores increased P21 expression. Trajectory revealed altered developmental dynamics PR, classical non-classical branches. Transcriptional EGR1 NFκB throughout progression, particularly PR. These findings reveal previously unrecognized features dysregulation provide potential therapeutic targets for treatment.

Language: Английский

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