Single-cell Multi-omics Analysis of Human Testicular Germ Cell Tumor Reveals its Molecular Features and Microenvironment

Seminoma is the most common malignant solid tumor in 14 to 44 year-old men. However, its molecular features and tumor microenvironment (TME) is largely unexplored. Here, we performed a series of studies via genomics profiling (single cell multi-omics and spatial transcriptomics) and functional examination using seminoma samples and a seminoma cell line. We identified key gene expression programs shared between seminoma and primordial germ cells, and further characterized the functions of TFAP2C in promoting tumor invasion and migration. We also identified 15 immune cell subtypes in TME, and found that subtypes with exhaustion features were located closer to the tumor region through combined spatial transcriptome analysis. Furthermore, we identified key pathways and genes that may facilitate seminoma breaking through the seminiferous tubules. These findings advanced our knowledge of seminoma tumorigenesis and produced a multi-omics atlas of in situ human seminoma microenvironment, which could help discover potential therapy targets for seminoma. scRNA-Seq 4 samples

精原细胞瘤（Seminoma）是14至44岁男性群体中最常见的恶性实体肿瘤。然而，其分子特征与肿瘤微环境（tumor microenvironment, TME）的相关研究仍存在大量未被探索的空白。本研究以精原细胞瘤样本与精原细胞瘤细胞系为研究材料，通过基因组谱分析（单细胞多组学（single cell multi-omics）与空间转录组学（spatial transcriptomics））及功能实验开展了一系列研究。我们鉴定出精原细胞瘤与原始生殖细胞共有的关键基因表达程序，并进一步阐明了TFAP2C在促进肿瘤侵袭与迁移中的功能。此外，我们在肿瘤微环境中鉴定出15种免疫细胞亚型，并通过联合空间转录组分析发现，具有免疫耗竭特征的免疫细胞亚型更贴近肿瘤区域。进一步而言，本研究还鉴定出可促进精原细胞瘤突破生精小管的关键通路与基因。本研究成果深化了学界对精原细胞瘤发生发展机制的认知，并构建了原位人精原细胞瘤微环境的多组学图谱，可为精原细胞瘤潜在治疗靶点的发现提供重要参考。本研究包含4份单细胞RNA测序（scRNA-Seq）样本。