单细胞基因组学和转录组学技术的最新进展已经转化了我们对于细胞异质性在生长、发育、衰老和疾病中的认识；但是，单细胞脂质组学的方法在发展方面相对落后。我们开发了一种方法，结合了荧光辅助细胞分选（FACS）、自动芯片纳米电喷雾离子化（nanoESI）和猎枪脂质组学，以检测和定量单个细胞中广泛的磷脂酰胆碱（PC）和鞘磷脂（SM）物种。我们在此展示，我们的方法能够量化50多个不同的PC和SM物种，并且能够轻松区分不同祖细胞系或受外源性脂肪酸处理的细胞。此外，我们的方法可以检测相同癌症类型的细胞系之间脂质组差异更微小的区别。我们的方法可以与其他单细胞技术并行运行，为具有相似表型的细胞提供几乎完整、高通量的多组学数据，并且具有大幅提升当前我们对于细胞异质性的认知的能力。版权所有 © 2023 The Authors，由Elsevier Inc.出版。保留所有权利。

Recent advances in single-cell genomics and transcriptomics technologies have transformed our understanding of cellular heterogeneity in growth, development, ageing and disease; however, methods for single-cell lipidomics have comparatively lagged behind in development. We have developed a method for the detection and quantification of a wide range of phosphatidylcholine (PC) and sphingomyelin (SM) species from single cells that combines fluorescence-assisted cell sorting (FACS) with automated chip-based nanoelectrospray ionization (nanoESI) and shotgun lipidomics. We show herein that our method is capable of quantifying more than 50 different PC and SM species from single cells and can easily distinguish between cells of different lineages or cells treated with exogenous fatty acids. Moreover, our method can detect more subtle differences in the lipidome between cell lines of the same cancer type. Our approach can be run in parallel with other single-cell technologies to deliver near-complete, high-throughput multi-omics data on cells with a similar phenotype and has the capacity to significantly advance our current knowledge on cellular heterogeneity.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.