Shi Zhongyu, Zhang Xuefei, Yang Huihui, Zheng Xiaolu, Niu Mengxiao, Zhang Yongjian, Yuan Pengfei, Wei Wensheng, Huang Gang, Fang Riguo, Chen Liangyi
EdiGene Inc., Beijing, China.
New Cornerstone Science Laboratory, National Biomedical Imaging Center, State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, School of Future Technology, Center for Life Sciences, Peking University, Beijing 100871, China.
Blood Sci. 2025 May 22;7(2):e00236. doi: 10.1097/BS9.0000000000000236. eCollection 2025 Jun.
Although changes in mitochondrial morphology consistently associated with the aging of hematopoietic stem cells (HSCs), the specific molecular and cellular mechanisms involved are partially unclear. Live-cell super-resolution (SR) microscopy has been used to identify distinct HSC subsets that characterized by mitochondria unique morphologies and spatial distributions. The integration of SR microscopy with single-cell RNA sequencing enabled the classification of approximately 200 HSCs from young and aged mice into 5 discrete clusters. These clusters displayed molecular profiles that corresponded to the observed mitochondria states. An integrated approach combining RNA biomarker analysis and potential regulon assessment revealed previously unrecognized roles of GDF15 in mediating mitochondrial signals and morphologies that influence HSC fate. Thus, combining SR imaging with a bioinformatics pipeline provides an effective method for identifying key molecular players in specific phases of cellular transition, even with a relatively small dataset.
尽管线粒体形态的变化一直与造血干细胞（HSC）的衰老相关，但其中涉及的具体分子和细胞机制仍部分不明。活细胞超分辨率（SR）显微镜已被用于识别以独特线粒体形态和空间分布为特征的不同HSC亚群。SR显微镜与单细胞RNA测序的结合，使得能够将来自年轻和老年小鼠的约200个HSC分类为5个离散簇。这些簇呈现出与观察到的线粒体状态相对应的分子特征。一种结合RNA生物标志物分析和潜在调控子评估的综合方法，揭示了生长分化因子15（GDF15）在介导影响HSC命运的线粒体信号和形态方面此前未被认识到的作用。因此，将SR成像与生物信息学流程相结合，即使使用相对较小的数据集，也能提供一种识别细胞转变特定阶段关键分子参与者的有效方法。
