Dissecting CAF subtypes in Pancreatic Cancer
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Within the stroma of pancreatic ductal adenocarcinoma (PDAC), mesenchymal cells differentiate into cancer-associated fibroblast (CAF) subtypes that differentially mediate disease progression. Defining the regulatory mechanism and diversity of CAF subtypes could identify potential therapeutic strategies to harness the tumor suppressive activities of CAFs. To address this, we utilized single-cell RNA sequencing to profile fibroblast activation protein-alpha (FAP) expressing mesenchymal cells in human PDAC. The mesenchymal subpopulations in PDAC reflected mesenchymal cell heterogeneity found in the normal developing pancreas. In addition to characterizing inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF) subpopulations in detail, the analysis uncovered a previously undescribed interferon-response CAF (ifCAF) subtype. Tumor-derived signals induced specific CAF subtypes from pancreatic stellate cells (PSCs) in an organoid-based co-culture model, and time-course experiments revealed regulatory mechanisms that govern subtype formation. STING agonists promoted an ifCAF phenotype in vivo and in vitro. Importantly, induction of an ifCAF phenotype suppressed tumor cell invasiveness and induced an anti-tumor phenotype in tumor-associated neutrophils. Together, this study resolves FAP+ stromal cell heterogeneity in PDAC and identifies an ifCAF subtype that can be induced to suppress pro-tumorigenic features of PDAC (Cumming et al., 2025). This dataset contains the following data and metadata files: 1. Six pairs of fastq files that contain the actual sequencing data. The total size is 230 GB. Each pair represents a paired-end single-cell RNA sequencing from an individual patient sample. The fastq files are text files with genomic sequence and sequence quality metrics. They are stored as compressed gzip-ed files. 2. A metadata file with sample information. The variables included are: Sample name, sequencing library ID, sequencing depth, sequencing index, number of cells, barcode set, patient pseudo ID (P1-P5), pathologic diagnosis, gender, age, surgical procedure, pathological classification, tumour location, histological status (desmoplasia). This is an Excel file (xlsx). 3. A metadata file with sample information according to the Federated European Genome-Phenome Archive Sweden (FEGA-sweden) template format. This is an Excel file (xlsx). 4. Twelve processed data tables with raw read (UMI) count; Six files for quality filtered cells, and six files with all cells. Each table corresponds to a separate sample. This corresponds to gene expression levels after mapping to the reference genome. The data is stored in MEX format, i.e. three tab-delimited text files in sparse matrix format. The files are compressed with gzip. 5. Two cell annotation tables for the single-cell data. The tables describe read count, gene count, cluster number, and cell type annotation for 30786/26733 single cells from the 6 samples described in the sample information metadata file. The tables are submitted as tab-delimited text files. 6. Two binary files written in R programming language containing an object readable by the Seurat package. The files contain processed data in the form of read count (i.e. gene expression levels) and also as transformed (normalized and scaled) data and analysis results. The files are in RDS format and can be loaded in R. For more information about the data files, please read the documentation files that accompany this data description. If you would like to submit a request to access data of this dataset, please read the document Readme_before_submission_of_an_access_request.
在胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）的间质中，间充质细胞会分化为癌症相关成纤维细胞（cancer-associated fibroblast, CAF）亚型，这些亚型对疾病进展发挥差异化调控作用。明确CAF亚型的调控机制与多样性，有望发掘利用CAF抑瘤活性的潜在治疗策略。为此，我们利用单细胞RNA测序（single-cell RNA sequencing）对人PDAC中表达成纤维细胞活化蛋白-α（fibroblast activation protein-alpha, FAP）的间充质细胞开展了转录组表征。PDAC中的间充质亚群反映了正常发育胰腺中存在的间充质细胞异质性。除了详细表征炎性CAF（inflammatory CAF, iCAF）和成肌纤维样CAF（myofibroblastic CAF, myCAF）亚群外，本分析还发现了此前未被报道的干扰素应答型CAF（interferon-response CAF, ifCAF）亚型。肿瘤来源的信号可在类器官共培养模型中由胰腺星状细胞（pancreatic stellate cells, PSCs）诱导产生特定CAF亚型，时序实验揭示了调控亚型形成的分子机制。STING激动剂在体内外均可诱导ifCAF表型。值得注意的是，ifCAF表型的诱导可抑制肿瘤细胞侵袭性，并在肿瘤相关中性粒细胞中诱导抗肿瘤表型。综上，本研究解析了PDAC中FAP+间质细胞的异质性，并鉴定出可被诱导以抑制PDAC促瘤特性的ifCAF亚型（Cumming等，2025）。 本数据集包含以下数据与元数据文件： 1. 六组双端fastq格式测序数据文件，总容量为230 GB。每组对应1例患者样本的双端单细胞RNA测序数据。fastq文件为包含基因组序列与序列质量指标的文本文件，以gzip压缩格式存储。 2. 1份含样本信息的元数据文件，包含的变量包括：样本名称、测序文库ID、测序深度、测序索引、细胞数量、条形码组、患者伪ID（P1-P5）、病理诊断、性别、年龄、手术方式、病理分型、肿瘤位置、组织学状态（间质纤维化，desmoplasia）。该文件为Excel（xlsx）格式。 3. 1份符合欧洲联邦基因组-表型组档案瑞典分会（Federated European Genome-Phenome Archive Sweden, FEGA-sweden）模板格式的样本信息元数据文件，同样为Excel（xlsx）格式。 4. 12张处理后的数据表格，包含原始读段（UMI）计数；其中6份为经质量过滤的细胞数据，6份为全部细胞数据。每张表格对应1份独立样本，对应参考基因组比对后的基因表达水平。数据以MEX格式存储，即包含三个制表符分隔的稀疏矩阵格式文本文件，且均以gzip压缩。 5. 2张单细胞数据的细胞注释表格，分别描述了来自上述6份样本的30786/26733个单细胞的读段计数、基因数量、聚类编号与细胞类型注释信息。表格以制表符分隔的文本文件形式提交。 6. 2份基于R语言编写的二进制文件，内含可被Seurat软件包读取的对象。文件包含读段计数（即基因表达水平）、经转化（标准化与缩放）后的数据及分析结果，格式为RDS，可在R环境中加载。 如需了解更多数据文件的相关信息，请查阅本数据说明随附的文档文件。如需提交本数据集的数据访问申请，请阅读《数据访问申请提交前必读》（"Readme_before_submission_of_an_access_request"）文档。
