Single-cell atlas of lineage states, tumor microenvironment and subtype specific expression programs in gastric cancer
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ABSTRACT:
PROVIDER: PRJNA762312 | ENA |
REPOSITORIES: ENA
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| S-EPMC9394383 | biostudies-literature
Project description:Gastric cancer (GC) heterogeneity between and within tumors represents a barrier to disease management. We generated a comprehensive single-cell atlas of GC comprising 31 primary gastric tumor samples representing clinical stages I-IV and histological subtypes. We identified 34 distinct cell-lineage states, related by developmental trajectories and previously unreported rare cell populations. Many lineage states exhibited a distinctive tumor-associated expression profile, each contributing individually to a combined tumor-wide molecular collage. We observed increased plasma cell proportions as a feature of diffuse-type tumors associated with epithelial-resident KLF2, and a stagewise accrual of novel cancer-associated fibroblast sub-populations marked by high INHBA and FAP co-expression. Our results provide a high-resolution molecular resource for GC translational studies, identifying intra- and inter-patient lineage-states across distinct GC subtypes. #### GEO title mapping with the ID in PMID:34642171 #### Manuscript_ID Primary_Tumor Primary_Normal Peritoneal_Tumor Peritoneal_Normal NGCII521 sample7.csv sample6.csv - - NGCII513 sample22.csv sample21.csv - - NGCII512 sample26.csv sample25.csv - - NGCII520 sample5.csv sample4.csv - - NGCII514 sample24.csv sample23.csv - - NGCII518 sample2.csv sample1.csv - - NGCII525 sample10.csv sample9.csv - - NGCII527 sample12.csv sample11.csv - - NGCII538 sample36.csv sample35.csv sample38.csv sample37.csv NGCII539 sample32.csv - - - NGCII529 sample13.csv - - - NGCII511 sample15.csv - - - NGCII498 sample18.csv - - - NGCII522 sample29.csv - - - NGCII499 sample16.csv - - - NGCII502 sample14.csv - - - NGCII509 sample17.csv - - - NGCII540 sample33.csv - - - NGCII541 sample34.csv - - - NGCII543 sample39.csv - - - NGCII510 sample27.csv - - - NGCII519 sample3.csv - - - NGCII531 sample28.csv - - - NGCII545 sample40.csv - - - NGCII533 sample30.csv - - - NGCII524 sample8.csv - - - NGCII536 - sample31.csv - - NGCII011 - - sample19.csv - NGCII015 - - sample20.csv -
2021-10-05 | GSE183904 | GEO
Project description:Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, the interaction of underlying signals driving distinct immune and stromal landscapes is still unclear. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma showed M1 recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.
2023-06-25 | GSE231535 | GEO
Project description:Coordinated single cell tumor microenvironment dynamics reinforce pancreatic cancer subtype
| PRJNA966248 | ENA
Project description:Single cell transcriptome atlas of microenvironment in preovulation follicle
| PRJNA785257 | ENA
Project description:Enhancer Transcription Reveals Subtype-Specific Transcription Programs Controlling Breast Cancer Pathogenesis
| PRJNA379949 | ENA
Project description:Primary cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin lymphomas. Outcomes for patients with advanced-stage disease are suboptimal, as few complete and durable responses are achieved with currently available therapeutic agents. However, improved understanding of oncogenic transcriptional programs in malignant T cells and their engagement with the tumor microenvironment (TME) may unveil therapeutic vulnerabilities. Therefore, we have compiled the largest available scRNA-seq CTCL atlas that includes >2 million skin and blood cells from 116 patients. We identified recurrent transcriptional programs in malignant T cells, a subset of which are associated with GATA-3 dependent transcriptional programs, especially in the setting of large cell transformation and advanced-stage disease. Many of the transcriptional programs identified are therapeutically targetable with clinically available agents, including HDAC, XPO1, JAK/CSF1R, and IKZF1/IKZF3 antagonists. The CTCL TME is dominated by infiltrating and exhausted effector and cytotoxic T cells that are restrained by a robust infiltrate of regulatory T cells (8%), transcriptionally polarized monocytes/macrophages (7%), and cancer-associated fibroblasts. Collectively, these findings have significant implications for the rationale design of combinatorial strategies targeting immune checkpoints, including PD-1. We have identified transcriptional programs, driven by oncogenic transcription factors, and constituents of the TME as therapeutic vulnerabilities in CTCL, and hope that the CTCL atlas constructed will provide a valuable resource for future studies exploiting these therapeutic vulnerabilities.
2026-06-10 | GSE309807 | GEO
Project description:Background Ampulla of Vater (AoV) carcinoma is a rare malignancy arising at the junction of intestinal and pancreatobiliary epithelium. Its heterogeneous clinical behavior and histological diversity have hindered therapeutic advances, and the cellular basis of this heterogeneity remains unclear. We aimed to construct a single-cell transcriptomic atlas of AoV carcinoma, with a focus on identifying epithelial subtypes and their interactions with the tumor microenvironment (TME). Methods We performed single-cell RNA sequencing on eight primary AoV tumors and four matched normal tissues. Comprehensive clustering and transcriptomic analyses identified cell-type composition, epithelial heterogeneity, and tumor-immune interactions. Findings were validated using deconvolution of bulk RNA-seq data from 62 AoV carcinoma patients. Results Malignant epithelial cells were categorized into four distinct subtypes: Int-Wnt, PB-KRAS, Int-Hypoxia, and Cycling stage. PB-KRAS cells exhibited stem-like transcriptional programs and high genomic instability. Deconvolution analysis of bulk RNA-seq data from the independent AoV cohort revealed that enrichment of the PB-KRAS subtype correlated with tumor recurrence and poor survival. Our immune profiling analysis discovered a significant association between PB-KRAS subtype and GZMK+ CD8+ T cells, which are in a pre-dysfunctional state, alongside SPP1⁺ macrophages exhibiting immunosuppressive traits. Spatial transcriptome data further supports the immunosuppressive natures of TME around PB-KRAS subtype malignant epithelial cells in AoV carcinoma. Conclusions Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.
2026-06-21 | GSE335070 | GEO
Project description:A single cell atlas of the human liver tumor microenvironment
| PRJNA610528 | ENA
Project description:Single-Cell Multimodal Atlas Reveals Regulatory Programs in the Human Brain
| PRJNA1449449 | ENA