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Tsutomu Masujima

Tsutomu Masujima

The Quantitative Biology Center (QBiC), RIKEN, Japan

Title: Single-cell metabolomics— Past, current, and future

Biography

Biography: Tsutomu Masujima

Abstract

Since cells behave individually, there needs to be a method to investigate cell metabolism at the single-cell or single-organelle level individually. Metabolites generate extensive peaks in mass spectrometry (MS), thus, these are good targets for analysis. However, even with this high sensitivity, single-cell metabolomics was hard to perform due to the tiny size of cells. The size of a typical mammalian cell is 10 µm; its volume is only 1 pico liter (pL). That may be the reason why only big cells, eggs, giant axons, and big plant cells, were the targets for the past single-cell metabolomics. Now, after live single-cell mass spectrometry has been proposed, in which 1 pL or less of single-cell content, or even an organelle, is directly sucked by a nanospray tip and fed into a MS after adding the ionization solvent. Hundreds to thousands of metabolite peaks are detected. These detected molecular peaks are aligned and analyzed using a t-test or principal component analysis to discern the specific identity of the cell or the precise internal location of the molecules. The peaks are finally annotated by MS/MS and/or data bases such as KEGG and MassBank. However, we should not be satisfied with this level of single-cell metabolomics. Metabolomics is only metabolomics. Metabolism may be the final stage of cellular activity along the journey of gene expression, but it is comprised of many necessary molecular mechanisms. Thus, we should improve single-cell metabolomics to be more comprehensive, i.e. detect not only the hydrophilic molecules but also the hydrophobic and neutral molecules. Furthermore, the method should be able to detect the activities of other molecules, such as proteins, mRNA, and DNA, to find essential pieces of molecular mechanisms. When we are able to understand what metabolomics is truly saying, metabolomics will become real metabolomics.