Abstract
Recent studies show that bioactive lipids are important regulators for stem cell survival and differentiation. The sphingolipid ceramide and its derivative, sphingosine-1-phosphate (S1P), can act synergistically on embryonic stem (ES) cell differentiation. We show here simple methods to analyze sphingolipids in differentiating ES cells and to use ceramide and S1P analogs for the guided differentiation of mouse ES cells toward neuronal and glial lineage.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Bieberich E, Silva J, Wang G, Krishnamurthy K, Condie BG (2004) Selective apoptosis of pluripotent mouse and human stem cells by novel ceramide analogues prevents teratoma formation and enriches for neural precursors in ES cell-derived neural transplants. J Cell Biol 167:723–734
Yanai J, Doetchman T, Laufer N, Maslaton J, Mor-Yosef S, Safran A, Shani M, Sofer D (1995) Embryonic cultures but not embryos transplanted to the mouse’s brain grow rapidly without immunosuppression. Int J Neurosci 81:21–26
Wakitani S, Takaoka K, Hattori T, Miyazawa N, Iwanaga T, Takeda S, Watanabe TK, Tanigami A (2003) Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint. Rheumatology (Oxford) 42:162–165
Teramoto K, Hara Y, Kumashiro Y, Chinzei R, Tanaka Y, Shimizu-Saito K, Asahina K, Teraoka H, Arii S (2005) Teratoma formation and hepatocyte differentiation in mouse liver transplanted with mouse embryonic stem cell-derived embryoid bodies. Transplant Proc 37:285–286
Swijnenburg RJ, Tanaka M, Vogel H, Baker J, Kofidis T, Gunawan F, Lebl DR, Caffarelli AD, de Bruin JL, Fedoseyeva EV, Robbins RC (2005) Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation 112:I166–I172
Sanchez-Pernaute R, Studer L, Ferrari D, Perrier A, Lee H, Vinuela A, Isacson O (2005) Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation. Stem Cells 23:914–922
Kim D, Gu Y, Ishii M, Fujimiya M, Qi M, Nakamura N, Yoshikawa T, Sumi S, Inoue K (2003) In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell. Pancreas 27:e34–e41
Fujikawa T, Oh SH, Pi L, Hatch HM, Shupe T, Petersen BE (2005) Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells. Am J Pathol 166:1781–1791
Fong SP, Tsang KS, Chan AB, Lu G, Poon WS, Li K, Baum LW, Ng HK (2007) Trophism of neural progenitor cells to embryonic stem cells: neural induction and transplantation in a mouse ischemic stroke model. J Neurosci Res 85:1851–1862
Choi D, Oh HJ, Chang UJ, Koo SK, Jiang JX, Hwang SY, Lee JD, Yeoh GC, Shin HS, Lee JS, Oh B (2002) In vivo differentiation of mouse embryonic stem cells into hepatocytes. Cell Transplant 11:359–368
Bielby RC, Boccaccini AR, Polak JM, Buttery LD (2004) In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng 10:1518–1525
Arnhold S, Klein H, Semkova I, Addicks K, Schraermeyer U (2004) Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Invest Ophthalmol Vis Sci 45:4251–4255
Baker M (2009) Stem cells: fast and furious. Nature 458:962–965
Leor J, Gerecht S, Cohen S, Miller L, Holbova R, Ziskind A, Shachar M, Feinberg MS, Guetta E, Itskovitz-Eldor J (2007) Human embryonic stem cell transplantation to repair the infarcted myocardium. Heart 93:1278–1284
Blum B, Benvenisty N (2008) The tumorigenicity of human embryonic stem cells. Adv Cancer Res 100:133–158
Lee AS, Tang C, Cao F, Xie X, van der Bogt K, Hwang A, Connolly AJ, Robbins RC, Wu JC (2009) Effects of cell number on teratoma formation by human embryonic stem cells. Cell Cycle 8:2608–2612
Fong CY, Gauthaman K, Bongso A (2010) Teratomas from pluripotent stem cells: a clinical hurdle. J Cell Biochem 111:769–781
Kuznetsov S, Cherman N, Gehron Robey P (2010) In vivo bone formation by progeny of human embryonic stem cells. Stem Cells Dev 20:269–287
Wang NK, Tosi J, Kasanuki JM, Chou CL, Kong J, Parmalee N, Wert KJ, Allikmets R, Lai CC, Chien CL, Nagasaki T, Lin CS, Tsang SH (2010) Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa. Transplantation 89:911–919
Bieberich E (2008) Smart drugs for smarter stem cells: making SENSe (sphingolipid-enhanced neural stem cells) of ceramide. Neurosignals 16:124–139
Bieberich E (2008) Ceramide signaling in cancer and stem cells. Future Lipidol 3:273–300
Bieberich E, Hu B, Silva J, MacKinnon S, Yu RK, Fillmore H, Broaddus WC, Ottenbrite RM (2002) Synthesis and characterization of novel ceramide analogs for induction of apoptosis in human cancer cells. Cancer Lett 181:55–64
Bieberich E, Kawaguchi T, Yu RK (2000) N-Acylated serinol is a novel ceramide mimic inducing apoptosis in neuroblastoma cells. J Biol Chem 275:177–181
Wang G, Krishnamurthy K, Umapathy NS, Verin AD, Bieberich E (2009) The carboxyl-terminal domain of atypical protein kinase Czeta binds to ceramide and regulates junction formation in epithelial cells. J Biol Chem 284:14469–14475
Wang G, Silva J, Krishnamurthy K, Tran E, Condie BG, Bieberich E (2005) Direct binding to ceramide activates protein kinase Czeta before the formation of a pro-apoptotic complex with PAR-4 in differentiating stem cells. J Biol Chem 280:26415–26424
Dutta D, Ray S, Home P, Larson M, Wolfe MW, Paul S (2011) Self renewal vs. lineage commitment of embryonic stem cells: protein kinase C signaling shifts the balance. Stem Cells 29(4):618–628 [epub ahead of print]
Bieberich E, MacKinnon S, Silva J, Noggle S, Condie BG (2003) Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide. J Cell Biol 162:469–479
Bieberich E, MacKinnon S, Silva J, Yu RK (2001) Regulation of apoptosis during neuronal differentiation by ceramide and b-series complex gangliosides. J Biol Chem 276:44396–44404
Bieberich E (2010) There is more to a lipid than just being a Fat: sphingolipid-guided differentiation of oligodendroglial lineage from embryonic stem cells. Neurochem Res 36(9):1601–1611 [epub ahead of print]
Hancock CR, Wetherington JP, Lambert NA, Condie BG (2000) Neuronal differentiation of cryopreserved neural progenitor cells derived from mouse embryonic stem cells. Biochem Biophys Res Commun 271:418–421
Westmoreland JJ, Hancock CR, Condie BG (2001) Neuronal development of embryonic stem cells: a model of GABAergic neuron differentiation. Biochem Biophys Res Commun 284:674–680
Okabe S, Forsberg-Nilsson K, Spiro AC, Segal M, McKay RD (1996) Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro. Mech Dev 59:89–102
Roach L, McNelsh JD (2002) Methods for the isolation and maintenance of murine embryonic stem cells. In: Turksen K (ed) Methods in molecular biology, vol 183, Embryonic stem cells. Humana, New Jersey, pp 1–16
Salli U, Fox TE, Carkaci-Salli N, Sharma A, Robertson GP, Kester M, Vrana KE (2009) Propagation of undifferentiated human embryonic stem cells with nano-liposomal ceramide. Stem Cells Dev 18:55–65
Krishnamurthy K, Wang G, Silva J, Condie BG, Bieberich E (2007) Ceramide regulates atypical PKC{zeta}/{lambda}-mediated cell polarity in primitive ectoderm cells: a novel function of sphingolipids in morphogenesis. J Biol Chem 282:3379–3390
Krishnamurthy K, Dasgupta S, Bieberich E (2007) Development and characterization of a novel anti-ceramide antibody. J Lipid Res 48:968–975
Acknowledgements
This study was in part supported by the NIH grants R01AG034389 and R01NS046835, a GRAVentureLab grant, and a March of Dimes grant 6-FY08-322.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Bieberich, E. (2012). Ceramide and Sphingosine-1-Phosphate Signaling in Embryonic Stem Cell Differentiation. In: Pébay, A., Turksen, K. (eds) Sphingosine-1-Phosphate. Methods in Molecular Biology, vol 874. Humana Press. https://doi.org/10.1007/978-1-61779-800-9_14
Download citation
DOI: https://doi.org/10.1007/978-1-61779-800-9_14
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-799-6
Online ISBN: 978-1-61779-800-9
eBook Packages: Springer Protocols