中国科学院分子细胞科学卓越创新中心周波、华东师范大学Jing-Jing Wan和上海交通大学Kun Qian团队合作的论文，在单细胞分辨率揭示了造血干细胞的代谢异质性。2024年1月2日出版的《细胞—代谢》杂志发表了这项成果。

研究人员研发了一个造血干细胞高通量单细胞代谢组学（hi-scMet）平台。通过将流式细胞分离和纳米粒子增强激光解吸/电离质谱技术相结合，研究人员从单细胞中检测到超过100个特征。研究绘制了所有造血细胞群和不同分裂时间造血干细胞亚群的单细胞代谢组图，检测到33个特征，其表达在造血干细胞增殖过程中呈现趋势性变化。

研究发现，从休眠期到活跃期，磷酸戊糖氧化途径（OxiPPP）被逐渐激活。基因或药物干扰OxiPPP会增加造血干细胞中的活性氧水平，从而降低氧化应激时造血干细胞的自我更新能力。总之，该研究揭示了造血干细胞增殖过程中的代谢动态，揭示了OxiPPP在造血干细胞活化过程中的作用，并证明了hi-scMet在免疫表型确细胞群的代谢异质性分析中的实用性。

据介绍，代谢状态对干细胞的功能至关重要；然而，内源性干细胞的代谢异质性从未得到过直接评估。

附：英文原文

Title: Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution

Author: Jing Cao, Qi Jason Yao, Jiao Wu, Xiaonan Chen, Lin Huang, Wanshan Liu, Kun Qian, Jing-Jing Wan, Bo O. Zhou

Issue&Volume: 2024/01/02

Abstract: Metabolic status is crucial for stem cell functions; however, the metabolic heterogeneityof endogenous stem cells has never been directly assessed. Here, we develop a platformfor high-throughput single-cell metabolomics (hi-scMet) of hematopoietic stem cells(HSCs). By combining flow cytometric isolation and nanoparticle-enhanced laser desorption/ionizationmass spectrometry, we routinely detected >100 features from single cells. We mappedthe single-cell metabolomes of all hematopoietic cell populations and HSC subpopulationswith different division times, detecting 33 features whose levels exhibited trendingchanges during HSC proliferation. We found progressive activation of the oxidativepentose phosphate pathway (OxiPPP) from dormant to active HSCs. Genetic or pharmacologicalinterference with OxiPPP increased reactive oxygen species level in HSCs, reducingHSC self-renewal upon oxidative stress. Together, our work uncovers the metabolicdynamics during HSC proliferation, reveals a role of OxiPPP for HSC activation, andillustrates the utility of hi-scMet in dissecting metabolic heterogeneity of immunophenotypicallydefined cell populations.

DOI: 10.1016/j.cmet.2023.12.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00456-4