Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 13, 2023

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays crucial role in remodeling the tumor microenvironment (TME). Here, through integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups CAFs described their distribution characteristics. Additionally, RNA sequencing (scRNA-seq) from three additional types two newly generated scRNA-seq datasets rare namely epithelial-myoepithelial carcinoma (EMC) mucoepidermoid (MEC), expanded our understanding CAF heterogeneity. Cell-cell interaction conducted within context highlighted pivotal roles matrix (mCAFs) angiogenesis inflammatory (iCAFs) shaping immunosuppressive microenvironment. In patients with breast (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity facilitating proliferation, promoting epithelial-mesenchymal transition (EMT), contributing to establishment an Furthermore, scoring system based on showed significant correlation immune therapy response melanoma patients. Lastly, provided web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for research community investigate pan-cancer.

Language: Английский

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An integrated single-cell reference atlas of the human endometrium

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(9), P. 1925 - 1937

Published: Aug. 28, 2024

The complex and dynamic cellular composition of the human endometrium remains poorly understood. Previous endometrial single-cell atlases profiled few donors lacked consensus in defining cell types. We introduce Human Endometrial Cell Atlas (HECA), a high-resolution reference atlas (313,527 cells) combining published new transcriptomics datasets 63 women with without endometriosis. HECA assigns identifies previously unreported types, mapped situ using spatial validated independent single-nuclei dataset (312,246 nuclei, donors). In functionalis, we identify intricate stromal-epithelial coordination via transforming growth factor beta (TGFβ) signaling. basalis, define signaling between fibroblasts an epithelial population expressing progenitor markers. Integration large-scale endometriosis genome-wide association study data pinpoints decidualized stromal cells macrophages as most likely dysregulated is valuable resource for studying physiology disorders, guiding microphysiological vitro systems development.

Language: Английский

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Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer

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

Published: March 22, 2024

Abstract Head and neck squamous cell carcinoma is the sixth most common cancer worldwide has high heterogeneity unsatisfactory outcomes. To better characterize tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous early-stage, advanced-stage lymph node, recurrent tumors tissue samples. We identify transcriptional development trajectory malignant epithelial cells a tumorigenic subcluster regulated by TFDP1 . Furthermore, find that infiltration POSTN + fibroblasts SPP1 macrophages gradually increases with progression; their interaction or also increase to shape desmoplastic microenvironment reprogram promote progression. Additionally, demonstrate during node metastasis, exhausted CD8 T CXCL13 expression strongly interact acquire more aggressive phenotypes extranodal expansion. Finally, delineate distinct features in primary tumors, providing theoretical foundation for precise selection targeted therapy at different stages. In summary, current study offers comprehensive landscape deep insight into microenvironmental reprogramming throughout initiation, progression, metastasis recurrence head carcinoma.

Language: Английский

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Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 12, 2024

Abstract Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify complex rare cell populations at single-cell resolution. By scRNA-seq, heterogeneity of tumor microenvironment across cervical carcinogenesis has mapped described. Whether these alterations could be detected applied to unclear. Herein, we performed scRNA-seq 56,173 exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade (HSIL), The present study delineated alteration immune epithelial derived during progression. A subset lipid-associated macrophage was identified as tumor-promoting element serve biomarker for predicting progression LSIL into HSIL, which then verified by immunofluorescence. Furthermore, cell–cell communication analysis indicated SPP1-CD44 axis might exhibit protumor interaction between macrophage. In this study, investigated multicellular ecosystem in potential biomarkers early detection.

Language: Английский

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Prognostic value of CDKN2A in head and neck squamous cell carcinoma via pathomics and machine learning

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(9)

Published: May 1, 2024

Abstract This study aims to enhance the prognosis prediction of Head and Neck Squamous Cell Carcinoma (HNSCC) by employing artificial intelligence (AI) analyse CDKN2A gene expression from pathology images, directly correlating with patient outcomes. Our approach introduces a novel AI‐driven pathomics framework, delineating more precise relationship between survival rates compared previous studies. Utilizing 475 HNSCC cases TCGA database, we stratified patients into high‐risk low‐risk groups based on thresholds. Through analysis 271 available slides, extracted 465 distinctive features construct Gradient Boosting Machine (GBM) model. model was then employed compute Pathomics scores (PS), predicting levels validation for accuracy pathway association analysis. demonstrates significant correlation higher improved median overall (66.73 months high vs. 42.97 low expression, p = 0.013), establishing CDKN2A's prognostic value. The pathomic exhibited exceptional predictive (training AUC: 0.806; 0.710) identified strong link cell cycle activation pathways. Validation through tissue microarray corroborated capacity our Confirming as crucial marker in HNSCC, this advances existing literature implementing an evaluation. innovative methodology offers cost‐efficient non‐invasive alternative traditional diagnostic procedures, potentially revolutionizing personalized medicine oncology.

Language: Английский

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Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: May 16, 2024

Introduction: Among the various stromal cell types within tumor microenvironment, cancer-associated fibroblasts (CAFs) emerge as predominant constituent, exhibiting a diverse array of oncogenic functions not intrinsic to normal fibroblasts. Their involvement spans across all stages tumorigenesis, encompassing initiation, progression, and metastasis. Current understanding posits coexistence distinct subpopulations CAFs microenvironment spectrum solid tumors, showcasing both pro- antitumor activities. Recent advancements in single-cell transcriptomics have revolutionized our ability meticulously dissect heterogeneity inherent CAF populations. Furthermore, accumulating evidence underscores pivotal role conferring therapeutic resistance tumors against drug modalities. Consequently, efforts are underway develop pharmacological agents specifically targeting CAFs. Methods: This review embarks on comprehensive analysis, consolidating data from 36 independent RNA sequencing investigations spanning 17 human malignant types. Results: Our exploration centers elucidating population markers, discerning their prognostic relevance, delineating functional contributions, underlying mechanisms orchestrating chemoresistance. Discussion: Finally, we deliberate potential harnessing promising targets for intervention strategies clinical oncology.

Language: Английский

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Single-cell RNA sequencing highlights the unique tumor microenvironment of small cell neuroendocrine cervical carcinoma

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Small cell neuroendocrine cervical carcinoma is a highly aggressive tumor characterized by early metastasis, high recurrence rate, and poor prognosis. This study represents the first instance of single-cell sequencing conducted on small cervix worldwide. Analysis gene expression regulatory networks revealed that transcription factor TFF3 drived up-regulation ELF3. Furthermore, our findings indicated marker genes associated with differed from those observed in lung, intestine, liver within GEO database, suggesting tissue-specific origins for these malignancies. Overall, this addresses significant research understanding vivo provides valuable insights guiding radiotherapy, chemotherapy, targeted therapy.

Language: Английский

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Investigating the role of exosomal long non-coding RNAs in drug resistance within female reproductive system cancers

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 24, 2025

Exosomes, as key mediators of intercellular communication, have been increasingly recognized for their role in the oncogenic processes, particularly facilitating drug resistance. This article delves into emerging evidence linking exosomal lncRNAs to modulation resistance mechanisms cancers such ovarian, cervical, and endometrial cancer. It synthesizes current research findings on how these influence cancer cell survival, tumor microenvironment, chemotherapy efficacy. Additionally, review highlights potential therapeutic strategies targeting lncRNAs, proposing a new frontier overcoming By mapping interface resistance, this aims provide comprehensive understanding that could pave way innovative treatments improved patient outcomes female reproductive system cancers.

Language: Английский

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Dissecting the Spatial and Single‐Cell Transcriptomic Architecture of Cancer Stem Cell Niche Driving Tumor Progression in Gastric Cancer

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

Published: Feb. 14, 2025

Abstract Despite significant advancements in identifying novel therapeutic targets and compounds, cancer stem cells (CSCs) remain pivotal driving resistance tumor progression gastric (GC). High‐resolution knowledge of the transcriptional programs underlying role CSC niche stemness is still lacking. Herein, spatial single‐cell RNA sequencing 32 human mucosa tissues at various stages malignancy, illuminating phenotypic plasticity epithelium trajectory from mature chief to state, which associated with activation EGFR WNT signaling pathways, conducted. Moreover, CSCs interact not only immunosuppressive CXCL13 + T CCL18 M2 macrophages evade immune surveillance, but also inflammatory cancer‐associated fibroblasts (iCAFs) promote tumorigenesis maintain stemness, construct leading inferior prognosis. Notably, it uncovered that amphiregulin (AREG) derived iCAFs promotes by upregulating expression SOX9 cells, contributes drug via AREG‐ERBB2 axis. This study provides valuable insight into characteristics progression, offering perspective for designing effective strategies overcome GC therapy resistance.

Language: Английский

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Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(12), P. 2175 - 2188

Published: Nov. 20, 2023

Language: Английский

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