Single-cell atlas of lineage states, tumor microenvironment and subtype specific expression programs in gastric cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA762312 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:A single cell atlas of the human liver tumor microenvironment
| PRJNA610528 | ENA
Project description:Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity. This intratumoral co-existence of classical and basal-like programs is evident in multi-scale transcriptomic and spatial analyses of resected, advanced-stage and chemotherapy-treated specimens and reciprocally linked to a diverse stromal immune microenvironment as well as worse clinical outcome. However, the underlying mechanisms of intratumoral subtype heterogeneity remain largely unclear. Here, by combining preclinical models, multi-center clinical, bulk and compartment-specific transcriptomic, proteomic, and bioimaging data from human specimens, we identified an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic CD68+ macrophages as a driver of intratumoral subtype co-existence along with an immunosuppressive tumor microenvironment with T cell exclusion. Our ATAC , ChIP-, and RNA-seq analyses revealed that JUNB/AP1- and HDAC-mediated epigenetic programs repress pro-inflammatory immune signatures in tumor cells, antagonizing cJUN/AP1 signaling to favor a therapy-responsive classical neoplastic identity. Through the tumor microenvironment, this dichotomous regulation was further amplified via regional macrophage populations. Moreover, CD68+/TNF-α+ cells associated with a reactive phenotype and reduced CD8+ T cell infiltration in human PDAC tumors. Consequently, combined anti-TNF-α immunotherapy and chemotherapy resulted in reduced macrophage counts and promoted CD3+/CD8+ T cell infiltration in basal-like PDAC, leading to improved survival in preclinical murine models. We conclude that tumor cell intrinsic epigenetic programs, together with extrinsic microenvironmental cues, facilitate intratumoral subtype heterogeneity and disease progression.
2023-12-31 | GSE245941 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity. This intratumoral co-existence of classical and basal-like programs is evident in multi-scale transcriptomic and spatial analyses of resected, advanced-stage and chemotherapy-treated specimens and reciprocally linked to a diverse stromal immune microenvironment as well as worse clinical outcome. However, the underlying mechanisms of intratumoral subtype heterogeneity remain largely unclear. Here, by combining preclinical models, multi-center clinical, bulk and compartment-specific transcriptomic, proteomic, and bioimaging data from human specimens, we identified an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic CD68+ macrophages as a driver of intratumoral subtype co-existence along with an immunosuppressive tumor microenvironment with T cell exclusion. Our ATAC , ChIP-, and RNA-seq analyses revealed that JUNB/AP1- and HDAC-mediated epigenetic programs repress pro-inflammatory immune signatures in tumor cells, antagonizing cJUN/AP1 signaling to favor a therapy-responsive classical neoplastic identity. Through the tumor microenvironment, this dichotomous regulation was further amplified via regional macrophage populations. Moreover, CD68+/TNF-α+ cells associated with a reactive phenotype and reduced CD8+ T cell infiltration in human PDAC tumors. Consequently, combined anti-TNF-α immunotherapy and chemotherapy resulted in reduced macrophage counts and promoted CD3+/CD8+ T cell infiltration in basal-like PDAC, leading to improved survival in preclinical murine models. We conclude that tumor cell intrinsic epigenetic programs, together with extrinsic microenvironmental cues, facilitate intratumoral subtype heterogeneity and disease progression.
2024-11-01 | GSE276322 | GEO
Project description:During development, the human brain orchestrates the generation of hundreds of diverse cell types, and recent transcriptomic atlases of the developing human cortex provide new opportunities to identify novel regulators of cell fate specification. We have conducted an integrated meta-analysis of seven recently published single-cell transcriptomic profiles of the developing human cortex, generating a meta-atlas of 225 meta-modules. By tracking the activity of these meta-modules throughout development and comparing this to datasets from the adult human as well as the developing and adult mouse, we identified modules with potential roles in the transition from neurogenesis to gliogenesis and neuronal subtype maturation. The cell type and developmental state at which these modules exist was validated in primary samples from the developing human brain. Of particular interest, we identified and validated a module associated with both developing human deep layer neurons and human adult deep layer neuronal subtypes expressing the terminal differentiation marker FEZF2. Though FEZF2 is neither a member of nor co-expressed with our deep layer-associated gene module, almost half of module genes are putative FEZF2 targets, including TSHZ3, a transcription factor associated with neurodevelopmental disorders such as autism. Knockdown experiments in human cortical organoid models confirm that both FEZF2 and TSHZ3 are necessary for deep layer neuron specification. Importantly, we observe that subtle manipulations of these transcription factors result in slight changes in module activity, but together yield strong differences in cell fate. Our analyses therefore reveal a gene network that required to generate deep layer neuronal subtypes, demonstrating the ability of our meta-atlas to engender further mechanistic analyses of cortical fate specification. We anticipate this resource being useful for the study of co-expression programs across diverse biological questions related to the developing neocortex.
2023-09-12 | GSE242779 | GEO
Project description:Differential programs of melanocyte cell states
| PRJNA975369 | ENA