TY - JOUR
T1 - Single-Cell and Subcellular Analysis Using Ultrahigh Resolution 21 T MALDI FTICR Mass Spectrometry
AU - Castro, Daniel C.
AU - Smith, Karl W.
AU - Norsworthy, Miles D.
AU - Rubakhin, Stanislav S.
AU - Weisbrod, Chad R.
AU - Hendrickson, Christopher L.
AU - Sweedler, Jonathan V.
N1 - This project was supported by the National Institute on Drug Abuse under Award no. P30DA018310, the National Human Genome Research Institute under Award no. R01HG010023, and the NSF National Research Traineeship on Miniature Brain Machinery NSF DGE 17-35252. The content is solely the responsibility of the authors and does not necessarily represent the official views of the awarding agencies. The ICR User Facility at the National High Magnetic Field Laboratory is supported by the National Science Foundation Division of Chemistry and Division of Materials Research through DMR-1644779, and the State of Florida.
PY - 2023/5/2
Y1 - 2023/5/2
N2 - The mammalian brain contains ∼20,000 distinct lipid species that contribute to its structural organization and function. The lipid profiles of cells change in response to a variety of cellular signals and environmental conditions that result in modulation of cell function through alteration of phenotype. The limited sample material combined with the vast chemical diversity of lipids makes comprehensive lipid profiling of individual cells challenging. Here, we leverage the resolving power of a 21 T Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer for chemical characterization of individual hippocampal cells at ultrahigh mass resolution. The accuracy of the acquired data allowed differentiation of freshly isolated and cultured hippocampal cell populations, as well as finding differences in lipids between the soma and neuronal processes of the same cell. Differences in lipids include TG 42:2 observed solely in the cell bodies and SM 34:1;O2 found only in the cellular processes. The work represents the first mammalian single cells analyzed at ultrahigh resolution and is an advance in the performance of mass spectrometry (MS) for single-cell research.
AB - The mammalian brain contains ∼20,000 distinct lipid species that contribute to its structural organization and function. The lipid profiles of cells change in response to a variety of cellular signals and environmental conditions that result in modulation of cell function through alteration of phenotype. The limited sample material combined with the vast chemical diversity of lipids makes comprehensive lipid profiling of individual cells challenging. Here, we leverage the resolving power of a 21 T Fourier-transform ion cyclotron resonance (FTICR) mass spectrometer for chemical characterization of individual hippocampal cells at ultrahigh mass resolution. The accuracy of the acquired data allowed differentiation of freshly isolated and cultured hippocampal cell populations, as well as finding differences in lipids between the soma and neuronal processes of the same cell. Differences in lipids include TG 42:2 observed solely in the cell bodies and SM 34:1;O2 found only in the cellular processes. The work represents the first mammalian single cells analyzed at ultrahigh resolution and is an advance in the performance of mass spectrometry (MS) for single-cell research.
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U2 - 10.1021/acs.analchem.3c00393
DO - 10.1021/acs.analchem.3c00393
M3 - Article
C2 - 37070980
AN - SCOPUS:85154027923
SN - 0003-2700
VL - 95
SP - 6980
EP - 6988
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 17
ER -