Wang Hailong, Wang Meng, Wang Bing, Zheng Lingna, Chen Hanqing, Chai Zhifang, Feng Weiyue
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B, Yu Quan Road, Shijingshan District, Beijing, 100049, China.
Anal Bioanal Chem. 2017 Feb;409(5):1415-1423. doi: 10.1007/s00216-016-0075-y. Epub 2016 Dec 1.
Cellular heterogeneity is an inherent condition of cell populations, which results from stochastic expression of genes, proteins, and metabolites. The heterogeneity of individual cells can dramatically influence cellular decision-making and cell fate. So far, our knowledge about how the variation of endogenous metals and non-metals in individual eukaryotic cells is limited. In this study, ICP-MS equipped with a high efficiency cell introduction system (HECIS) was developed as a method of single-cell ICP-MS (SC-ICP-MS). The method was applied to the single-cell analysis of Mn, Fe, Co, Cu, Zn, P, and S in human cancer cell lines (HeLa and A549) and normal human bronchial epithelial cell line (16HBE). The analysis showed obvious variation of the masses of Cu, Fe, Zn, and P in individual HeLa cells, and variation of Fe, Zn, and P in individual A549 cells. On the basis of the single-cell data, a multimodal distribution of the elements in the cell population was fitted, which showed marked differences among the various cell lines. Importantly, subpopulations of the elements were found in the cell populations, especially in the HeLa cancer cells. This study demonstrates that SC-ICP-MS is able to unravel the extent of variation of endogenous elements in individual cells, which will help to improve our fundamental understanding of cellular biology and reveal novel insights into human biology and medicine. Graphical abstract The variations of masses and distribution patterns of elements Mn, Fe, Co, Cu, Zn, P, and S in single cells were successfully detected by ICP-MS coupled with a high efficiency cell introduction system (HECIS).
细胞异质性是细胞群体的一种内在状态，它源于基因、蛋白质和代谢物的随机表达。单个细胞的异质性可显著影响细胞决策和细胞命运。到目前为止，我们对单个真核细胞内源性金属和非金属变化情况的了解有限。在本研究中，配备高效细胞引入系统（HECIS）的电感耦合等离子体质谱仪（ICP-MS）被开发为一种单细胞ICP-MS（SC-ICP-MS）方法。该方法应用于人类癌细胞系（HeLa和A549）及正常人支气管上皮细胞系（16HBE）中锰、铁、钴、铜、锌、磷和硫的单细胞分析。分析显示，单个HeLa细胞中铜、铁、锌和磷的质量存在明显差异，单个A549细胞中铁、锌和磷也有差异。基于单细胞数据，拟合了细胞群体中元素的多峰分布，结果表明不同细胞系之间存在显著差异。重要的是，在细胞群体中发现了元素亚群，尤其是在HeLa癌细胞中。本研究表明，SC-ICP-MS能够揭示单个细胞内源性元素的变化程度，这将有助于增进我们对细胞生物学的基本理解，并揭示人类生物学和医学的新见解。图形摘要 通过ICP-MS与高效细胞引入系统（HECIS）联用，成功检测了单细胞中锰、铁、钴、铜、锌、磷和硫元素的质量变化及分布模式。
