title: Interrogating the variation of element masses and distribution patterns in single cells using ICP-MS with a high efficiency cell introduction system.
abstract: 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).
authors.affiliation: 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.
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Lingna
authors.initials: L
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Chai
authors.affiliation: 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. fengwy@ihep.ac.cn.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Feng
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D014131:Trace Elements / Q000032:analysis*
chemical_list: D014131:Trace Elements
keywords: Endogenous elements; Human cell lines; Single-cell ICP-MS; Single-cell analysis; Subpopulation; Variation