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科学家绘制出人类鳞状细胞癌组成和空间结构的多模式图谱
作者:小柯机器人 发布时间:2020/6/28 10:25:18

美国斯坦福大学医学院Paul A. Khavari小组绘制出人类鳞状细胞癌组成和空间结构的多模式图谱。2020年6月23日,《细胞》杂志在线发表了这一最新研究成果。

为了定义皮肤鳞状细胞癌(cSCC)的细胞组成和结构,研究人员将单细胞RNA测序与空间转录组学和来自一系列人类cSCC和配对正常皮肤的多重离子束成像相结合。cSCC具有四个肿瘤亚群,三个涵盖了正常表皮状态的群体以及一个肿瘤特异性角质形成细胞(TSK)群体,后者定位于纤维血管微环境中。单细胞和空间数据映射的配体-受体网络与特定细胞类型的整合,揭示了TSK细胞是细胞间通讯的枢纽。
 
研究人员观察到免疫抑制的多种特征,包括在分隔的肿瘤基质中与CD8 T细胞共定位的调节性T细胞(Treg)。最后,人类肿瘤异种移植物的单细胞表征和体内CRISPR筛选确定了特定肿瘤亚群富集基因网络在肿瘤发生中的重要作用。这些数据定义了cSCC肿瘤和基质细胞亚群、它们相互作用的空间微环境以及它们在癌症中参与的交流基因网络。
 
附:英文原文

Title: Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma

Author: Andrew L. Ji, Adam J. Rubin, Kim Thrane, Sizun Jiang, David L. Reynolds, Robin M. Meyers, Margaret G. Guo, Benson M. George, Annelie Mollbrink, Joseph Bergenstrhle, Ludvig Larsson, Yunhao Bai, Bokai Zhu, Aparna Bhaduri, Jordan M. Meyers, Xavier Rovira-Clavé, S. Tyler Hollmig, Sumaira Z. Aasi, Garry P. Nolan, Joakim Lundeberg, Paul A. Khavari

Issue&Volume: 2020-06-23

Abstract: To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.

DOI: 10.1016/j.cell.2020.05.039

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30672-3

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/