Non-invasive Optical Biomarkers Distinguish and Track the Metabolic Status of Single Hematopoietic Stem Cells
Hao Zhou,
Lisa Nguyen,
Cosimo Arnesano,
Yuta Ando,
Manmeet Raval,
Joseph T. Rodgers,
Scott Fraser,
Rong Lu,
Keyue Shen
Affiliations
Hao Zhou
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
Lisa Nguyen
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA
Cosimo Arnesano
Translational Imaging Center, University of Southern California, Los Angeles, CA 90089, USA; Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
Yuta Ando
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA
Manmeet Raval
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA
Joseph T. Rodgers
Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA
Scott Fraser
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; Translational Imaging Center, University of Southern California, Los Angeles, CA 90089, USA; Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
Rong Lu
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Keyue Shen
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; USC Stem Cell, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Summary: Metabolism is a key regulator of hematopoietic stem cell (HSC) functions. There is a lack of real-time, non-invasive approaches to evaluate metabolism in single HSCs. Using fluorescence lifetime imaging microscopy, we developed a set of metabolic optical biomarkers (MOBs) from the auto-fluorescent properties of metabolic coenzymes NAD(P)H and FAD. The MOBs revealed the enhanced glycolysis, low oxidative metabolism, and distinct mitochondrial localization of HSCs. Importantly, the fluorescence lifetime of enzyme-bound NAD(P)H (τbound) can non-invasively monitor the glycolytic/lactate dehydrogenase activity in single HSCs. As a proof of concept for metabolism-based cell sorting, we further identified HSCs within the Lineage-cKit+Sca1+ (KLS) hematopoietic stem/progenitor population using MOBs and a machine-learning algorithm. Moreover, we revealed the dynamic changes of MOBs, and the association of longer τbound with enhanced glycolysis under HSC stemness-maintaining conditions during HSC culture. Our work thus provides a new paradigm to identify and track the metabolism of single HSCs non-invasively and in real time. : Optical Imaging; Biological Sciences; Cellular Physiology; Stem Cells Research Subject Areas: Optical Imaging, Biological Sciences, Cellular Physiology, Stem Cells Research
