人細胞毒性T細胞單細胞代謝譜的揭示
作者：
小柯機器人發布時間：2020/9/2 16:14:30
美國史丹福大學Sean C. Bendall小組揭示了人細胞毒性T細胞的單細胞代謝譜。該項研究成果在線發表在2020年8月31日出版的《自然-生物技術》上
在本研究中，研究人員開發了一種可表徵單細胞代謝規律及其表型特徵的方法。該方法稱為單細胞代謝調節圖譜（scMEP），其基於高維抗體技術對調節代謝途徑的活性蛋白質進行定量。利用大規模細胞計數法（飛行時間細胞計數法，CyTOF）對scMEP在大量代謝測定時進行基準測試，研究人員重塑了體外激活條件下初始和記憶CD8+ T細胞的代謝。
將該方法應用於臨床樣本，研究人員在人大腸癌中鑑定了組織特異性、代謝抑制的細胞毒性T細胞。將該方法與飛行時間多重離子束成像相結合（MIBI-TOF），研究人員揭示了人體組織中代謝基序的空間組織，並表明代謝抑制的免疫細胞被排除在腫瘤免疫之外。總的來說，該方法可實現單個細胞中代謝和功能狀態的匹配。
研究人員表示，細胞代謝調節免疫細胞的活化、分化和效應子功能，但是目前的代謝方法不能實現單細胞解析度和細胞表型的同時表徵。
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