Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 505 South Goodwin Avenue, Urbana, Illinois 61801, United States.
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, Illinois 61801, United States.
Anal Chem. 2023 May 2;95(17):6980-6988. doi: 10.1021/acs.analchem.3c00393. Epub 2023 Apr 18.
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.
哺乳动物的大脑包含约 20000 种不同的脂质种类，这些脂质种类有助于大脑的结构组织和功能。细胞的脂质谱会响应各种细胞信号和环境条件而发生变化，从而通过改变表型来调节细胞功能。有限的样本材料加上脂质的巨大化学多样性，使得对单个细胞进行全面的脂质分析具有挑战性。在这里，我们利用 21T 傅里叶变换离子回旋共振（FTICR）质谱仪的分辨率，对单个海马细胞进行超高质量分辨率的化学特征分析。所获得数据的准确性允许区分新鲜分离和培养的海马细胞群体，以及发现同一细胞的体部和神经元突起之间的脂质差异。差异脂质包括仅在细胞体中观察到的 TG 42:2 和仅在细胞突起中发现的 SM 34:1;O2。这项工作代表了首次在超高分辨率下分析哺乳动物单细胞，是质谱（MS）在单细胞研究中的一项进展。
