Abstract
Phospholipids are classified into glycerophospholipids and sphingolipids, which are lipid bilayer components and act as a source of various bioactive substances and signal transducers. Stem cells undergo dynamic morphological changes during differentiation, and the metabolism of phospholipids in these cells also changes significantly. Similarly, during reprogramming, cells undergo significant morphological alterations, accompanied by changes in phospholipids. Furthermore, changes in the metabolism and composition of phospholipids due to external factors induce cell differentiation, while changes in the composition of phospholipids affect the reprogramming of cells. Mass spectrometry has shown that phospholipids in tissue regeneration and repair and disease are metabolized differently at specific sites in the tissue. Regarding cell polarity at the single-cell level, phospholipids bind to particular proteins and contribute to the determination of cell polarity and apical-basal polarity in epithelia. The synthesis of phospholipids is mediated by mutual transport and synthesis between mitochondria and the endoplasmic reticulum, and abnormalities in mitochondria phospholipid metabolism are also involved in cell transformation. This chapter will review phospholipid metabolism and its application to disease analysis using stem cells.
Abbreviations
- DAG:
-
Diacylglycerol
- DHB:
-
2,5 dihydroxybenzoic acid
- ESC:
-
Embryonic stem cells
- ESI:
-
Electrospray ionization
- FIA:
-
Flow injection analysis
- HPLC:
-
High-performance liquid chromatography
- LC-MS:
-
Liquid chromatography-mass spectrometry
- LTQ:
-
Linear ion trap
- MALDI-TOF/TOF-IMS:
-
Matrix-assisted laser desorption/ionization -time-of-flight/−imaging mass spectrometry
- PC:
-
Phosphatidylcholine
- PS:
-
Phosphatidylserine
- PI:
-
Phosphatidylinositol
- PA:
-
Phosphatidic acid
- PG:
-
Phosphatidylglycerol
- QTOF:
-
Quadrupole time-of-flight
- QTRAP:
-
Quadrupole/linear ion trap
- SM:
-
Sphingomyelin
- UPLC:
-
Ultra performance liquid chromatography
- UHPLC:
-
Ultra high-performance liquid chromatography
References
Bozelli JC Jr, Epand RM (2021) Plasmalogen replacement therapy. Membranes (Basel) 11:838. https://doi.org/10.3390/membranes11110838
Clémot M, Sênos Demarco R, Jones DL (2020) Lipid mediated regulation of adult stem cell behavior. Front Cell Dev Biol 8:115. https://doi.org/10.3389/fcell.2020.00115
Dean JM, Lodhi IJ (2018) Structural and functional roles of ether lipids. Protein Cell 9:196–206. https://doi.org/10.1007/s13238-017-0423-5
Fader Kaiser CM, Romano PS, Vanrell MC, Pocognoni CA, Jacob J, Caruso B, Delgui LR (2022) Biogenesis and breakdown of lipid droplets in pathological conditions. Front Cell Dev Biol 9:826248. https://doi.org/10.3389/fcell.2021.826248
Fakoya AOJ, Omole AE, Satyadev N, Haider HK (2022) Induced pluripotent stem cells: progress towards clinical translation from bench to bedside. In: Haider KH (ed) Handbook of stem cell therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_31-1
Henne M, Goodman JM, Hariri H (2020) Spatial compartmentalization of lipid droplet biogenesis. Biochim Biophys Acta Mol Cell Biol Lipids 1865(1):158499. https://doi.org/10.1016/j.bbalip.2019.07.008
Ibrahim AY, Mehdi Q, Abbas AO, Alashkar A, Haider KH (2016) Induced pluripotent stem cells: next generation cells for tissue regeneration. J Biomed Sci Eng 9(4):226–244
Jackson AO, Tang H, Yin K (2020) HiPS-cardiac Trilineage cell generation and transplantation: a novel therapy for myocardial infarction. J Cardiovasc Transl Res 13:110–119. https://doi.org/10.1007/s12265-019-09891-4
Kiamehr M, Viiri LE, Vihervaara T, Koistinen KM, Hilvo M, Ekroos K, Käkelä R et al (2017) Lipidomic profiling of patient-specific iPSC-derived hepatocyte-like cells. Dis Model Mech 10:1141–1153. https://doi.org/10.1242/dmm.030841
Klein O, Strohschein K, Nebrich G, Fuchs M, Thiele H, Giavalisco P, Duda G et al (2018) Unraveling local tissue changes within severely injured skeletal muscles in response to MSC-based intervention using MALDI imaging mass spectrometry. Sci Rep 8:12677. https://doi.org/10.1038/s41598-018-30990-w
Koch J, Watschinger K, Werner ER, Keller MA (2022) Tricky isomers-the evolution of analytical strategies to characterize plasmalogens and plasmanyl ether lipids. Front Cell Dev Biol 10:864716. https://doi.org/10.3389/fcell.2022.864716
Krahn MP (2020) Phospholipids of the plasma membrane – regulators or consequence of cell polarity? Front Cell Dev Biol 8:277. https://doi.org/10.3389/fcell.2020.00277
Lee J, Yeganeh B, Ermini L, Post M (2015) Sphingolipids as cell fate regulators in lung development and disease. Apoptosis 20:740–757. https://doi.org/10.1007/s10495-015-1112-6
Leibel SL, Tseu I, Zhou A, Hodges A, Yin J, Bilodeau C, Goltsis O, Post M (2022) Metabolomic profiling of human pluripotent stem cell differentiation into lung progenitors. iScience 25:103797. https://doi.org/10.1016/j.isci.2022.103797
Liu X, Flinders C, Mumenthaler SM, Hummon AB (2018) MALDI mass spectrometry imaging for evaluation of therapeutics in colorectal tumor organoids. J Am Soc Mass Spectrom 29:516–526. https://doi.org/10.1007/s13361-017-1851-4
Meissen JK, Yuen BT, Kind T, Riggs JW, Barupal DK, Knoepfler PS, Fiehn O (2012) Induced pluripotent stem cells to show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism. PLoS One 7:e46770. https://doi.org/10.1371/journal.pone.0046770
Meng Y, Cheng X, Wang T, Hang W, Li X, Nie W, Liu R et al (2020) Micro-lensed fiber laser desorption mass spectrometry imaging reveals subcellular distribution of drugs within single cells. Angew Chem Int Ed Engl 59:17864–17871. https://doi.org/10.1002/anie.202002151
Miyamura N, Nakamura T, Goto-Inoue N, Zaima N, Hayasaka T, Yamasaki T et al (2011) Imaging mass spectrometry reveals characteristic changes in triglyceride and phospholipid species in regenerating mouse liver. Biochem Biophys Res Commun 408:120–125. https://doi.org/10.1016/j.bbrc.2011.03.133
Nakamura Y, Shimizu Y, Horibata Y, Tei R, Koike R, Masawa M, Watanabe T et al (2017) Changes of plasmalogen phospholipid levels during differentiation of induced pluripotent stem cells 409B2 to endothelial phenotype cells. Sci Rep 7:9377. https://doi.org/10.1038/s41598-017-09980-x
Nikitina A, Huang D, Li L, Peterman N, Cleavenger SE, Fernández FM, Kemp ML (2020) A co-registration pipeline for multimodal MALDI and confocal imaging analysis of stem cell colonies. J Am Soc Mass Spectrom 31:986–989. https://doi.org/10.1021/jasms.9b00094
Pappritz K, Klein O, Dong F, Hamdani N, Kovacs A, O’Flynn L, Elliman S et al (2021) MALDI-IMS as a tool to determine the myocardial response to Syndecan-2-selected mesenchymal stromal cell application in an experimental model of diabetic cardiomyopathy. Proteomics Clin Appl 15:e2000050. https://doi.org/10.1002/prca.202000050
Park JW, Park WJ, Futerman AH (2014) Ceramide synthases as potential targets for therapeutic intervention in human diseases. Biochim Biophys Acta 1841:671–681. https://doi.org/10.1016/j.bbalip.2013.08.019
Piroli ME, Blanchette JO, Jabbarzadeh E (2019) Polarity as a physiological modulator of cell function. Front Biosci (Landmark Ed) 24(3):451–462. https://doi.org/10.2741/4728. PMID: 30468666; PMCID: PMC6343491
Prieto J, GarcÃa-Cañaveras JC, León M, Sendra R, Ponsoda X, Izpisúa Belmonte JC, Lahoz A et al (2021) C-MYC triggers lipid remodelling during early somatic cell reprogramming to pluripotency. Stem Cell Rev Rep 17:2245–2261. https://doi.org/10.1007/s12015-021-10239-2
Rawicz W, Smith BA, McIntosh TJ, Simon SA, Evans E (2008) Elasticity, strength, and water permeability of bilayers that contain raft microdomain-forming lipids. Biophys J 94:4725–4736. https://doi.org/10.1529/biophysj.107.121731
Rocha B, Cillero-Pastor B, Eijkel G, Bruinen AL, Ruiz-Romero C, Heeren RM, Blanco FJ (2015) Characterization of lipidic markers of chondrogenic differentiation using mass spectrometry imaging. Proteomics 15:702–713. https://doi.org/10.1002/pmic.201400260
Shimizu Y, Satou M, Hayashi K, Nakamura Y, Fujimaki M, Horibata Y, Ando H et al (2017) Matrix-assisted laser desorption/ionization imaging mass spectrometry reveals changes of phospholipid distribution in induced pluripotent stem cell colony differentiation. Anal Bioanal Chem 409:1007–1016. https://doi.org/10.1007/s00216-016-0015-x
Shimizu Y, Nakamura Y, Horibata Y, Fujimaki M, Hayashi K, Uchida N, Morita H et al (2020) Imaging of lysophosphatidylcholine in an induced pluripotent stem cell-derived endothelial cell network. Regen Ther 14:299–305. https://doi.org/10.1016/j.reth.2020.03.007
Spruill ML, Maletic-Savatic M, Martin H, Li F, Liu X (2022) Spatial analysis of drug absorption, distribution, metabolism, and toxicology using mass spectrometry imaging. Biochem Pharmacol 201:115080. https://doi.org/10.1016/j.bcp.2022.115080
Sugimoto M, Shimizu Y, Yoshioka T, Wakabayashi M, Tanaka Y, Higashino K, Numata Y, Sakai S, Kihara A, Igarashi Y, Kuge Y (2015) Histological analyses by matrix-assisted laser desorption/ionization-imaging mass spectrometry reveal differential localization of sphingomyelin molecular species regulated by particular ceramide synthase in mouse brains. Biochim Biophys Acta 1851(12):1554–1565. https://doi.org/10.1016/j.bbalip.2015.09.004. Epub 2015 Oct 1. PMID: 26398595
Surrati AI, Haider KH, Sottile V (2020) Non-destructive metabolomics characterization of mesenchymal stem cell differentiation. In: Haider KH (ed) Stem cells: from hype to hope. World Scientific, Singapore
Tsogtbaatar E, Landin C, Minter-Dykhouse K, Folmes CDL (2020) Energy metabolism regulates stem cell pluripotency. Front Cell Dev Biol 8:87. https://doi.org/10.3389/fcell.2020.00087
van IJzendoorn SCD, Agnetti J, Gassama-Diagne A (2020) Mechanisms behind the polarized distribution of lipids in epithelial cells. Biochim Biophys Acta Biomembr 1862:183145. https://doi.org/10.1016/j.bbamem.2019.183145
van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124. https://doi.org/10.1038/nrm2330
Vance JE, Vance DE (2004) Phospholipid biosynthesis in mammalian cells. Biochem Cell Biol 82:113–128. https://doi.org/10.1139/o03-073
Wildburger NC, Wood PL, Gumin J, Lichti CF, Emmett MR, Lang FF, Nilsson CL (2015) ESI-MS/MS and MALDI-IMS localization reveal alterations in phosphatidic acid, diacylglycerol, and DHA in glioma stem cell xenografts. J Proteome Res 14:2511–2519. https://doi.org/10.1021/acs.jproteome.5b00076
Wu Y, Chen K, **ng G, Li L, Ma B, Hu Z, Duan L et al (2019) Phospholipid remodeling is critical for stem cell pluripotency by facilitating the mesenchymal-to-epithelial transition. Sci Adv 5:eaax7525. https://doi.org/10.1126/sciadv.aax7525
Yanes O, Clark J, Wong DM, Patti GJ, Sánchez-Ruiz A, Benton HP, Trauger SA et al (2010) Metabolic oxidation regulates embryonic stem cell differentiation. Nat Chem Biol 6:411–417. https://doi.org/10.1038/nchembio
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Shimizu, Y. (2024). Phospholipid Metabolism in Stem Cells and Its Application to the Pathophysiological Analysis. In: Haider, K.H. (eds) Handbook of Stem Cell Applications. Springer, Singapore. https://doi.org/10.1007/978-981-99-7119-0_45
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