单细胞转录组学揭示卵巢癌肉瘤的组织结构

Junfen Xu, Y. Cen, Weiguo Lu
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引用次数: 0

摘要

卵巢varian癌肉瘤(OCS)是卵巢癌中最罕见和最具挑战性的组织学亚型之一。它具有显著的细胞异质性。利用单细胞RNA测序,我们表征了OCS的细胞组成,并鉴定了它们的分子特征。方法采用单细胞RNA测序(scRNA-seq)技术对切除的原发OCS进行肿瘤细胞及TME的深入分析。采用免疫组织化学(IHC)染色进行验证。结果恶性上皮细胞和成纤维细胞表现出高度的瘤内异质性。我们发现某些上皮细胞亚群具有高水平的耐药评分和许多活跃的代谢途径。此外,γδ T细胞表现出丰富的IFNγ和IFNα反应特征。值得注意的是,我们观察到巨噬细胞主要是具有免疫抑制特性的m2样巨噬细胞。此外,我们发现CD1A+/FCER1A+ DC细胞富含与细胞溶解效应通路相关的基因。通过分析细胞类型之间的配体-受体相互作用对,我们确定了广泛相互作用的细胞,并观察到ANXA1+上皮细胞群与FPR1+/FPR3+骨髓细胞之间的相互作用。结论本研究提供了一个完整的人类OCS单细胞转录组图谱,为阐明OCS多样性提供了一个完善的资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-Cell Transcriptomics Reveals Tissue Architecture in Ovarian Carcinosarcoma
Background Ovarian carcinosarcoma (OCS) is one of rarest and most challenging histologic subtype of ovarian cancer. It features remarkable cellular heterogeneity. Using single-cell RNA sequencing, we characterize the cellular composition of the OCS and identify their molecular characteristics. Methods we applied single-cell RNA sequencing (scRNA-seq) to resected primary OCS for the in-depth analysis of tumor cells and the TME. Immunohistochemistry (IHC) staining was used for validation. Results Malignant epithelial and fibroblast cells displayed a high-degree of intratumoral heterogeneity. We revealed that certain epithelial cell subclusters had high levels of drug resistance scores and many active metabolic pathways. Furthermore, γδ T cells exhibited enriched IFNγ and IFNα response characteristics. Notably, we observed that macrophages were mainly M2-like macrophages with immunosuppressive properties. In addition, we found that the CD1A+/FCER1A+ DC cells were enriched with genes related to cytolytic effector pathway. Analyzing ligand-receptor interaction pairs between cell types, we identified broadly interacting cells and observed an interaction between the ANXA1+ epithelial population and FPR1+/FPR3+ myeloid cells. Conclusion Our findings provide a comprehensive single-cell transcriptomic landscape of human OCS and present a well-established resource for elucidating OCS diversity.
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