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

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Non-invasive Optical Biomarkers Distinguish and Track the Metabolic Status of Single Hematopoietic Stem Cells.
iScience ( IF 4.6 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.isci.2020.100831
Hao Zhou ₁ , Lisa Nguyen ₂ , Cosimo Arnesano ₃ , Yuta Ando ₁ , Manmeet Raval ₂ , Joseph T Rodgers ₂ , Scott Fraser ₄ , Rong Lu ₅ , Keyue Shen ₆

Affiliation

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.
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.
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.
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.

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.

中文翻译：

非侵入性光学生物标志物区分和追踪单个造血干细胞的代谢状态。

代谢是造血干细胞（HSC）功能的关键调节剂。缺乏评估单个HSC代谢的实时，非侵入性方法。使用荧光寿命成像显微镜，我们从代谢辅酶NAD（P）H和FAD的自发荧光特性开发了一组代谢光学生物标记（MOB）。MOBs揭示了HSCs的糖酵解增强，低氧化代谢和独特的线粒体定位。重要的是，酶结合的NAD（P）H（τ_结合的）的荧光寿命）可以无创地监测单个HSC中的糖酵解/乳酸脱氢酶活性。作为基于代谢的细胞分选概念的证明，我们进一步使用MOB和机器学习算法在Lineage-cKit + Sca1 +（KLS）造血干/祖细胞群中鉴定了HSC。此外，我们揭示了在HSC培养过程中，在保持HSC干性的条件下，MOB的动态变化以及更长的τ_结合与增强的糖酵解的关系。因此，我们的工作提供了一种新的范例，可以无创地实时识别和跟踪单个HSC的代谢。

更新日期：2020-01-10

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