Over the past years, plenty of evidence has emerged illustrating how metabolism supports many aspects of cellular function and how metabolic reprogramming can drive cell differentiation and fate. Here, we present a method to assess the metabolic configuration of single cells within their native tissue microenvironment via the visualization and quantification of multiple enzymatic activities measured at saturating substrate conditions combined with subsequent cell type identification. After careful validation of the approach and to demonstrate its potential, we assessed the intracellular metabolic configuration of different human immune cell populations in healthy and tumor colon tissue. Additionally, we analyzed the intercellular metabolic relationship between cancer cells and cancer-associated fibroblasts in a breast cancer tissue array. This study demonstrates that the determination of metabolic configurations in single cells could be a powerful complementary tool for every researcher interested to study metabolic networksin situ.

中文翻译：

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探索复杂组织微环境中单细胞的代谢构型

在过去的几年中，已经出现了大量的证据，说明了新陈代谢如何支持细胞功能的许多方面，以及新陈代谢的重新编程如何驱动细胞分化和命运。在这里，我们提出了一种方法，通过在饱和底物条件下测定的多种酶活性的可视化和定量以及随后的细胞类型鉴定，评估其天然组织微环境中单细胞的代谢构型。经过仔细验证该方法并证明其潜力后，我们评估了健康和肿瘤结肠组织中不同人类免疫细胞群的细胞内代谢构型。此外，我们分析了乳腺癌组织阵列中癌细胞与癌症相关成纤维细胞之间的细胞间代谢关系。