title: Identifying Metabolic Subpopulations from Population Level Mass Spectrometry.
abstract: Metabolism underlies many important cellular decisions, such as the decisions to proliferate and differentiate, and defects in metabolic signaling can lead to disease and aging. In addition, metabolic heterogeneity can have biological consequences, such as differences in outcomes and drug susceptibilities in cancer and antibiotic treatments. Many approaches exist for characterizing the metabolic state of a population of cells, but technologies for measuring metabolism at the single cell level are in the preliminary stages and are limited. Here, we describe novel analysis methodologies that can be applied to established experimental methods to measure metabolic variability within a population. We use mass spectrometry to analyze amino acid composition in cells grown in a mixture of (12)C- and (13)C-labeled sugars; these measurements allow us to quantify the variability in sugar usage and thereby infer information about the behavior of cells within the population. The methodologies described here can be applied to a large range of metabolites and macromolecules and therefore have the potential for broad applications.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: DeGennaro
authors.affiliation: Department of Physiology, Biophysics and Systems Biology, Faculty of Medicine, Technion, Haifa, 31096, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Savir
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, 02115, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Springer
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000502:physiology; D002478:Cells, Cultured / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods*; D055442:Metabolome; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids