Journal: bioRxiv
Article Title: Cross-species single-cell atlases chart progression, therapy-driven remodelling and immune evasion in pancreatic cancer
doi: 10.64898/2026.03.19.712924
Figure Lengend Snippet: a) Schematic overview of the experimental design. Mouse PDAC cell lines were clonally barcoded using a lentiviral library (1), expanded and orthotopically transplanted into syngeneic immunocompetent mice (2–3), followed by scRNA-seq profiling of resultant tumours (4). Expressed barcode tracing enabled unambiguous separation of malignant (TAG⁺) from host-derived non-malignant cells (right panel, UMAPs depicting barcoded (TAG + ) (top) and malignant (bottom) cells). b-e) UMAPs of the integrated Mouse PDAC Atlas coloured by dataset (b), sex (c), treatment type (d), and model (orthotopic syngeneic immunocompetent allografts vs. autochthonous GEMMs (e). f) Sample-wise cell-type composition across treatment types, datasets, and models. Autochthonous tumours were dominated by classical epithelial-like malignant states, whereas orthotopic allografts displayed greater heterogeneity with an enrichment of EMT, hypoxic, and mesenchymal programs. g ) Level 3 hierarchical annotation of the Mouse Atlas using the same multi-tiered scheme as the Human Atlas, resolving lymphoid, myeloid, stromal, endocrine, exocrine, endothelial, and malignant compartments. h-j) Substate resolution of major immune and stromal lineages: CD4⁺ T cells (h), CD8⁺ T cells (i), and macrophages (j), showing distinct regulatory, effector, angiogenic, and lipid-processing programs. k) Validation of double-positive (DP) CD4⁺CD8⁺ T cells at the transcriptomics level (transcription density plots, left panel) and at the protein level by flow cytometry (right panel). l) UMAP showing DP T cells coloured by species (left) and Pearson correlation of mouse DP T cell gene expression against the human DP T cell archetype (right).
Article Snippet: For clonal and state-fate analysis by single-cell RNA-seq, primary mouse PDAC cells were clonally tagged with expressed DNA barcodes using the LARRY Barcode Library (Addgene #140024; RRID: Addgene 140024) .
Techniques: Derivative Assay, Biomarker Discovery, Transcriptomics, Flow Cytometry, Gene Expression
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