德国欧洲分子生物学实验室Theodore Alexandrov、德国癌症研究中心Mathias Heikenwalder等研究人员合作开发出揭示单个细胞代谢状态的新方法。这一研究成果于2021年7月5日在线发表在国际学术期刊《自然—方法学》上。
研究人员开发了SpaceM，这是一种用于原位单细胞代谢组学的开源方法，每小时可从>1,000个单个细胞中检测>100种代谢物，以及基于荧光的读数和形态空间特征的保留。研究人员通过预测共培养的人上皮细胞和小鼠成纤维细胞的细胞类型验证了SpaceM。研究人员使用SpaceM来证明用脂肪酸刺激人类肝细胞会导致出现两种共存的亚群，这些亚群由不同的细胞代谢状态勾勒出来。
在依赖于NF-κB信号传导的过程中，用细胞因子白细胞介素17A诱导炎症会扰乱这些状态的平衡。在非酒精性脂肪性肝炎的小鼠模型中重现了这些代谢状态标记物。研究人员预计SpaceM将广泛适用于各种细胞模型的研究并使单细胞代谢组学简便化。
据悉，对细胞代谢重要性的日益认识以及关于细胞间异质性程度的揭示，需要对单个细胞进行代谢表征。
附：英文原文
Title: SpaceM reveals metabolic states of single cells
Author: Luca Rappez, Mira Stadler, Sergio Triana, Rose Muthoni Gathungu, Katja Ovchinnikova, Prasad Phapale, Mathias Heikenwalder, Theodore Alexandrov
Issue&Volume: 2021-07-05
Abstract: A growing appreciation of the importance of cellular metabolism and revelations concerning the extent of cell–cell heterogeneity demand metabolic characterization of individual cells. We present SpaceM, an open-source method for in situ single-cell metabolomics that detects >100 metabolites from >1,000 individual cells per hour, together with a fluorescence-based readout and retention of morpho-spatial features. We validated SpaceM by predicting the cell types of cocultured human epithelial cells and mouse fibroblasts. We used SpaceM to show that stimulating human hepatocytes with fatty acids leads to the emergence of two coexisting subpopulations outlined by distinct cellular metabolic states. Inducing inflammation with the cytokine interleukin-17A perturbs the balance of these states in a process dependent on NF-κB signaling. The metabolic state markers were reproduced in a murine model of nonalcoholic steatohepatitis. We anticipate SpaceM to be broadly applicable for investigations of diverse cellular models and to democratize single-cell metabolomics.
DOI: 10.1038/s41592-021-01198-0
Source: https://www.nature.com/articles/s41592-021-01198-0
Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex
本期文章：《自然—方法学》：Online/在线发表
