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

doi:10.1016/j.isci.2020.100831

Non-invasive Optical Biomarkers Distinguish and Track the Metabolic Status of Single Hematopoietic Stem Cells

iScience. 2020 Feb 21;23(2):100831. doi: 10.1016/j.isci.2020.100831. Epub 2020 Jan 10.

Authors

Hao Zhou¹, Lisa Nguyen², Cosimo Arnesano³, Yuta Ando¹, Manmeet Raval², Joseph T Rodgers², Scott Fraser⁴, Rong Lu⁵, Keyue Shen⁶

Affiliations

¹ Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
² Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033, USA.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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. Electronic address: keyue.shen@usc.edu.

Abstract

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 (τ_bound) 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 τ_bound 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.

Keywords: Biological Sciences; Cellular Physiology; Optical Imaging; Stem Cells Research.

Abstract

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