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人细胞毒性T细胞单细胞代谢谱的揭示
作者:小柯机器人 发布时间:2020/9/2 16:14:30

美国斯坦福大学Sean C. Bendall小组揭示了人细胞毒性T细胞的单细胞代谢谱。该项研究成果在线发表在2020年8月31日出版的《自然-生物技术》上

在本研究中,研究人员开发了一种可表征单细胞代谢规律及其表型特征的方法。该方法称为单细胞代谢调节图谱(scMEP),其基于高维抗体技术对调节代谢途径的活性蛋白质进行定量。利用大规模细胞计数法(飞行时间细胞计数法,CyTOF)对scMEP在大量代谢测定时进行基准测试,研究人员重塑了体外激活条件下初始和记忆CD8+ T细胞的代谢。

将该方法应用于临床样本,研究人员在人大肠癌中鉴定了组织特异性、代谢抑制的细胞毒性T细胞。将该方法与飞行时间多重离子束成像相结合(MIBI-TOF),研究人员揭示了人体组织中代谢基序的空间组织,并表明代谢抑制的免疫细胞被排除在肿瘤免疫之外。总的来说,该方法可实现单个细胞中代谢和功能状态的匹配。

研究人员表示,细胞代谢调节免疫细胞的活化、分化和效应子功能,但是目前的代谢方法不能实现单细胞分辨率和细胞表型的同时表征。

附:英文原文

Title: Single-cell metabolic profiling of human cytotoxic T cells

Author: Felix J. Hartmann, Dunja Mrdjen, Erin McCaffrey, David R. Glass, Noah F. Greenwald, Anusha Bharadwaj, Zumana Khair, Sanne G. S. Verberk, Alex Baranski, Reema Baskar, William Graf, David Van Valen, Jan Van den Bossche, Michael Angelo, Sean C. Bendall

Issue&Volume: 2020-08-31

Abstract: Cellular metabolism regulates immune cell activation, differentiation and effector functions, but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. In this study, we developed an approach to characterize the metabolic regulome of single cells together with their phenotypic identity. The method, termed single-cell metabolic regulome profiling (scMEP), quantifies proteins that regulate metabolic pathway activity using high-dimensional antibody-based technologies. We employed mass cytometry (cytometry by time of flight, CyTOF) to benchmark scMEP against bulk metabolic assays by reconstructing the metabolic remodeling of in vitro-activated naive and memory CD8+ T cells. We applied the approach to clinical samples and identified tissue-restricted, metabolically repressed cytotoxic T cells in human colorectal carcinoma. Combining our method with multiplexed ion beam imaging by time of flight (MIBI-TOF), we uncovered the spatial organization of metabolic programs in human tissues, which indicated exclusion of metabolically repressed immune cells from the tumor–immune boundary. Overall, our approach enables robust approximation of metabolic and functional states in individual cells. An antibody-based method enables profiling of metabolic protein expression and regulation in single cells using mass spectrometry.

DOI: 10.1038/s41587-020-0651-8

Source: https://www.nature.com/articles/s41587-020-0651-8

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:31.864
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex