ArticleJournal of biomedical optics2012
Label-free separation of human embryonic stem cells and their differentiating progenies by phasor fluorescence lifetime microscopy.
Article in Journal of biomedical optics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Deep Learning-Guided Holotomography Reveals Early Structural Remodelling During Pluripotency Exit.bioRxiv : the preprint server for biology · 2026Article
- Femtosecond label-free imaging evaluates the metabolism of mesenchymal stromal cells.Human cell · 2026Article
- A fluorescence lifetime separation approach for FLIM live-cell imaging.Journal of microscopy · 2026Article
- C1q drives neural stem cell quiescence by regulating cell cycle and metabolism through BAI1.Nature communications · 2025Article
- Two-photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure.Scientific reports · 2025Article
- Emerging Functional Connections Between Metabolism and Epigenetic Remodeling in Neural Differentiation.Molecular neurobiology · 2024Review
- Label-Free Optical Metabolic Imaging in Cells and Tissues.Annual review of biomedical engineering · 2023Review
- Phasor Analysis of Fluorescence Lifetime Enables Quantitative Multiplexed Molecular Imaging of Three Probes.Analytical chemistry · 2022Article
- Linear Combination Properties of the Phasor Space in Fluorescence Imaging.Sensors (Basel, Switzerland) · 2022Review
- Complex wavelet filter improves FLIM phasors for photon starved imaging experiments.Biomedical optics express · 2021Article
- A Review of New High-Throughput Methods Designed for Fluorescence Lifetime Sensing From Cells and Tissues.Frontiers in physics · 2021Article
- Advances in fluorescence microscopy techniques to study kidney function.Nature reviews. Nephrology · 2021Review
- Fluorescence lifetime imaging microscopy: fundamentals and advances in instrumentation, analysis, and applications.Journal of biomedical optics · 2020Review
- Multiphoton FLIM imaging of NAD(P)H and FAD with one excitation wavelength.Journal of biomedical optics · 2020Article
- Determination of the metabolic index using the fluorescence lifetime of free and bound nicotinamide adenine dinucleotide using the phasor approach.Journal of biophotonics · 2019Article
- NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival.Molecular biology of the cell · 2019Article
- Label-free assessment of pre-implantation embryo quality by the Fluorescence Lifetime Imaging Microscopy (FLIM)-phasor approach.Scientific reports · 2019Article
- Autofluorescence lifetime imaging of cellular metabolism: Sensitivity toward cell density, pH, intracellular, and intercellular heterogeneity.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2019Article
- Fluorescence lifetime shifts of NAD(P)H during apoptosis measured by time-resolved flow cytometry.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2019Article
- Fit-free analysis of fluorescence lifetime imaging data using the phasor approach.Nature protocols · 2018Article
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4 authors.
Funding
Abstract
We develop a label-free optical technique to image and discriminate undifferentiated human embryonic stem cells (hESCs) from their differentiating progenies in vitro. Using intrinsic cellular fluorophores, we perform fluorescence lifetime microscopy (FLIM) and phasor analysis to obtain hESC metabolic signatures. We identify two optical biomarkers to define the differentiation status of hESCs: Nicotinamide adenine dinucleotide (NADH) and lipid droplet-associated granules (LDAGs). These granules have a unique lifetime signature and could be formed by the interaction of reactive oxygen species and unsaturated metabolic precursor that are known to be abundant in hESC. Changes in the relative concentrations of these two intrinsic biomarkers allow for the discrimination of undifferentiated hESCs from differentiating hESCs. During early hESC differentiation we show that NADH concentrations increase, while the concentration of LDAGs decrease. These results are in agreement with a decrease in oxidative phosphorylation rate. Single-cell phasor FLIM signatures reveal an increased heterogeneity in the metabolic states of differentiating H9 and H1 hESC colonies. This technique is a promising noninvasive tool to monitor hESC metabolism during differentiation, which can have applications in high throughput analysis, drug screening, functional metabolomics and induced pluripotent stem cell generation.
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Registered trials
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