1. Multiparametric platform for profiling lipid trafficking in human leukocytes
- Author
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Simon G. Pfisterer, Ivonne Brock, Kristiina Kanerva, Iryna Hlushchenko, Lassi Paavolainen, Pietari Ripatti, Mohammad Majharul Islam, Aija Kyttälä, Maria D. Di Taranto, Annalisa Scotto di Frega, Giuliana Fortunato, Johanna Kuusisto, Peter Horvath, Samuli Ripatti, Markku Laakso, Elina Ikonen, Pfisterer, S. G., Brock, I., Kanerva, K., Hlushchenko, I., Paavolainen, L., Ripatti, P., Islam, M. M., Kyttala, A., Di Taranto, M. D., Scotto di Frega, A., Fortunato, G., Kuusisto, J., Horvath, P., Ripatti, S., Laakso, M., Ikonen, E., Department of Anatomy, STEMM - Stem Cells and Metabolism Research Program, Institute for Molecular Medicine Finland, Bioimage Profiling, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Helsinki Institute of Life Science HiLIFE, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Faculty Common Matters (Faculty of Social Sciences), and Lipid Trafficking Lab
- Subjects
Cultural Studies ,History ,obesity ,Literature and Literary Theory ,high-content imaging ,hypercholesterolemia ,automated image analysis ,lipid droplet ,LDL uptake ,FH ,LDL ,LDLR ,1182 Biochemistry, cell and molecular biology ,3111 Biomedicine ,automated image analysi - Abstract
Summary Systematic insight into cellular dysfunction can improve understanding of disease etiology, risk assessment, and patient stratification. We present a multiparametric high-content imaging platform enabling quantification of low-density lipoprotein (LDL) uptake and lipid storage in cytoplasmic droplets of primary leukocyte subpopulations. We validate this platform with samples from 65 individuals with variable blood LDL-cholesterol (LDL-c) levels, including familial hypercholesterolemia (FH) and non-FH subjects. We integrate lipid storage data into another readout parameter, lipid mobilization, measuring the efficiency with which cells deplete lipid reservoirs. Lipid mobilization correlates positively with LDL uptake and negatively with hypercholesterolemia and age, improving differentiation of individuals with normal and elevated LDL-c. Moreover, combination of cell-based readouts with a polygenic risk score for LDL-c explains hypercholesterolemia better than the genetic risk score alone. This platform provides functional insights into cellular lipid trafficking and has broad possible applications in dissecting the cellular basis of metabolic disorders.
- Published
- 2022
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