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Single-cell transcriptomics of precursor lung adenocarcinoma reveals intratumoral heterogeneity and shifting immune network

ABSTRACT: We conducted a multi-omics analysis including single-cell RNA transcriptome, single-cell T cell receptor (scTCR), whole exome sequencing and multiplex immunohistochemistry (mIHC) to decipher single cell atlas of precursor lung adenocarcinoma and mechanisms of diverse immune cells during precursor lesions development in hopes of digging out potential therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164789 | GEO | 2024/01/13

REPOSITORIES: GEO

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Single-Cell Transcriptomic Analysis of mIHC Images via Antigen Mapping

Project description:Highly-multiplexed immunohistochemistry (mIHC) enables the staining and quantification of dozens of antigens in a tissue section with single-cell resolution. However, annotating cell populations that differ little in the profiled antigens or for which the antibody panel does not include specific markers is challenging. To overcome this obstacle, we have developed an approach for enriching mIHC images with single-cell RNA-seq data, building upon recent experimental procedures for augmenting single-cell transcriptomes with concurrent antigen measurements. Spatially-resolved Transcriptomics via Epitope Anchoring (STvEA) performs transcriptome-guided annotation of highly-multiplexed cytometry datasets. It increases the level of detail in histological analyses by enabling annotation of subtle cell populations, spatial patterns of transcription, and interactions between cell types. More generally, it enables the systematic annotation of cell populations in cytometry data. We demonstrate the utility of STvEA by uncovering the architecture of poorly characterized cell types in the murine spleen using published highly-multiplexed cytometry and mIHC data.

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Single-Cell Transcriptomic Analysis of mIHC Images via Antigen Mapping

Project description:Single-Cell Transcriptomic Analysis of mIHC Images via Antigen Mapping

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Intratumoral heterogeneity, cell of origin and microenvironment in retinoblastoma [scRNA-seq]

Project description:Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. The diverse malignant and immune cells in tumors determine tumor progression, but the intratumoral heterogeneity, tumor microenvironment and their impact in RB remain poorly characterized. Here, we conducted transcriptomic profiles of around 70,000 cells from tumor samples of seven RB patients with pathological and clinical measurements. Fifteen cell types were identified where the majority were cone precursor-like (CP-like) and MKI67+ cone precursor (MKI67+ CP) cells. These cells expressed markers of cone precursor, suggesting that RB originated from cone precursor cells. The conversion of CP-like to MKI67+ CP led to the loss of photoreceptor function and increased cell proliferation ability in RB. By integrative copy number variation analysis, we found that two subtypes of MKI67+ CP cells were more malignant related to cell proliferation. The tumor microenvironment in RB was composed of three cell types, of which glial cells, including tumor-associated macrophages and astrocytes-like cells, created an immunosuppressive environment and promoted tumor growth and invasion by inhibiting the GALECTIN signaling pathway. Together, our study presents the first transcriptomic map of RB at a single-cell resolution and provides novel insights into the occurrence and progression of RB which will be important to the development of the future targeted therapy and immunotherapy.

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Homo sapiens

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Massively multiplex single-cell Hi-C

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Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features in Breast Cancer

Project description:Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive breast cancer. Its biological features, particularly its intratumoral heterogeneity, remain obscure. Moreover, mechanism of lymph node metastasis is unclear. To address this deficiency, we performed single-cell transcriptome profiling of DCIS, invasive ductal carcinoma (IDC) and lymph node metastasis. Single-cell transcriptome analysis revealed that breast cancer exhibits intratumoral heterogeneity at the transcriptional level, defining specific functions, and that DCIS has similar heterogeneity to IDC.

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Project description:Chronic viral infection results in CD8 T cell exhaustion. Here, we use paired single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) to investigate CD8 T cell phenotypic and clonal heterogeneity in multiple mice during the late stage of LCMV Clone 13 infection.

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2021-01-29 | GSE162499 | GEO

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