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Embryonic Stem Cells: The Role of Nitric Oxide in Regulating Cell Differentiation, Self-Renewal, and Apoptosis

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Stem Cells and Cancer Stem Cells,Volume 3

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 3))

Abstract

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been proclaimed as a source of undifferentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson’s disease, Fanconi’s anemia and diabetes. In addition to their potential in regenerative therapy, an understanding of the mechanisms by which these cells differentiate into any functional cell type will provide valuable information about basic biology. Screens for small compounds that can drive self-renewal maintenance or differentiation protocols are relevant to this goal. Nitric oxide (NO) is a diffusible second messenger implicated in numerous physiological functions in mammals. This molecule plays an important role in the maintenance of key features required for embryonic development and extension in ES cells. The goal of this chapter is to discuss recent advances concerning the ways in which NO signaling pathways mediate diverse mechanisms involved in the differentiation of ES cells toward multiple lineages. This chapter will also discuss the mechanisms by which NO can modify tissue-specific gene expression thorough chromatin remodeling and post-translational modification of transcription factors.

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References

  • Adamo L, Naveiras O, Wenzel PL, McKinney-Freeman S, Mack PJ, Gracia-Sancho J, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, Garcia-Cardena G, Daley GQ (2009) Biomechanical forces promote embryonic haematopoiesis. Nature 459:1131–1135

    Article  PubMed  CAS  Google Scholar 

  • Arnhold S, Fassbender A, Klinz FJ, Kruttwig K, Lohnig B, Andressen C, Addicks K (2002) NOS-II is involved in early differentiation of murine cortical, retinal and ES cell-derived neurons-an immunocytochemical and functional approach. Int J Dev Neurosci 20:83–92

    Article  PubMed  CAS  Google Scholar 

  • Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher AG (2006) Chromatin signatures of pluripotent cell lines. Nat Cell Biol 8:532–538

    Article  PubMed  CAS  Google Scholar 

  • Bloch W, Fleischmann BK, Lorke DE, Andressen C, Hops B, Hescheler J, Addicks K (1999) Nitric oxide synthase expression and role during cardiomyogenesis. Cardiovasc Res 43:675–684

    Article  PubMed  CAS  Google Scholar 

  • Choi BM, Pae HO, Jang SI, Kim YM, Chung HT (2002) Nitric oxide as a pro-apoptotic as well as anti-apoptotic modulator. J Biochem Mol Biol 35:116–126

    Article  PubMed  CAS  Google Scholar 

  • Danalache BA, Paquin J, Donghao W, Grygorczyk R, Moore JC, Mummery CL, Gutkowska J, Jankowski M (2007) Nitric oxide signaling in oxytocin-mediated cardiomyogenesis. Cell Mol Biol 25:679–688

    CAS  Google Scholar 

  • Enikolopov G, Banerji J, Kuzin B (1999) Nitric oxide and Drosophila development. Cell Death Differ 6:956–963

    Article  PubMed  CAS  Google Scholar 

  • Gassanov N, Jankowski M, Danalache B, Wang D, Grygorczyk R, Hoppe UC, Gutkowska J (2007) Arginine vasopressin-mediated cardiac differentiation: insights into the role of its receptors and nitric oxide signaling. J Biol Chem 282:11255–11265

    Article  PubMed  CAS  Google Scholar 

  • Gouge RC, Marshburn P, Gordon BE, Nunley W, Huet-Hudson YM (1998) Nitric oxide as a regulator of embryonic development. Biol Reprod 58:875–879

    Article  PubMed  CAS  Google Scholar 

  • Huang NF, Fleissner F, Sun J, Cooke JP (2010) Role of nitric oxide signaling in endothelial differentiation of embryonic stem cells. Stem Cells Dev 19:1617–1626

    Article  PubMed  CAS  Google Scholar 

  • Kanno S, Kim PK, Sallam K, Lei J, Billiar TR, Shears L (2004) Nitric oxide facilitates cardiomyogenesis in mouse embryonic stem cells. Proc Natl Acad Sci USA 101:12277–12281

    Google Scholar 

  • Korneev SA, Korneeva EI, Lagarkova MA, Kiselev SL, Critchley G, O’Shea M (2008) Novel noncoding antisense RNA transcribed from human anti-NOS2A locus is differentially regulated during neuronal differentiation of embryonic stem cells. RNA 14:2030–2037

    Article  PubMed  CAS  Google Scholar 

  • Krumenacker JS, Katsuki S, Kots A, Murad F (2006) Differential expression of genes involved in cGMP-dependent nitric oxide signaling in murine embryonic stem (ES) cells and ES cell-derived cardiomyocytes. Nitric Oxide 14:1–11

    Article  PubMed  CAS  Google Scholar 

  • Li T, Somasundaram J, Bian C, Xiong K, Mahmooduddin W, Nath F, Murad RK, F., 2010. Nitric oxide signaling and neural stem cell differentiation in peripheral nerve regeneration. Eplasty 10:e42.

    Google Scholar 

  • Madhusoodanan K, Murad F (2007) NO-cGMP signaling and regenerative medicine involving stem cells. Neurochem Res 32:681–694

    Google Scholar 

  • Malan D, Wenzel D, Schmidt A, Geisen C, Raible A, Bolck B, Fleischmann BK, Bloch W (2010) Endothelial beta1 integrins regulate sprouting and network formation during vascular development. Development 137:993–1002

    Article  PubMed  CAS  Google Scholar 

  • Mannick J (2006) Regulation of cell signaling by protein nitrosylation/denitrosylation.. In: Santiago Lamas EC (ed) Nitric oxide cell signaling, and gene expression. Taylor and Francis Group LLC, Los Angeles, CA, p 430

    Google Scholar 

  • McCloskey KE, Smith DA, Jo H, Nerem RM (2006) Embryonic stem cell-derived endothelial cells may lack complete functional maturation in vitro. J Vasc Res 43:411–421

    Article  PubMed  Google Scholar 

  • Miao L, Wang M, Yin WX, Yuan Q, Chen YX, Fleischmann B, Hescheler J, Ji G (2010) Atrial natriuretic peptide regulates Ca channel in early developmental cardiomyocytes. PLoS One 5:e8847

    Article  PubMed  Google Scholar 

  • Mora-Castilla S, Tejedo JR, Hmadcha A, Cahuana GM, Martin F, Soria B, Bedoya FJ (2010) Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation. Cell Death Differ 17:1025–1033

    Article  PubMed  CAS  Google Scholar 

  • Mujoo K, Krumenacker JS, Wada Y, Murad F (2006) Differential expression of nitric oxide signaling components in undifferentiated and differentiated human embryonic stem cells. Stem Cells Dev 15:779–787

    Article  PubMed  CAS  Google Scholar 

  • Mujoo K, Sharin VG, Bryan NS, Krumenacker JS, Sloan C, Parveen S, Nikonoff LE, Kots AY, Murad F (2008) Role of nitric oxide signaling components in differentiation of embryonic stem cells into myocardial cells. Proc Natl Acad Sci USA 105:18924–18929

    Google Scholar 

  • Nakamura T, Wang L, Wong CC, Scott FL, Eckelman BP, Han X, Tzitzilonis C, Meng F, Gu Z, Holland EA, Clemente AT, Okamoto S, Salvesen GS, Riek R, Yates JR 3rd, Lipton SA (2010) Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Mol Cell 39:184–195

    Article  PubMed  CAS  Google Scholar 

  • Nott A, Riccio A (2009) Nitric oxide-mediated epigenetic mechanisms in developing neurons. Cell Cycle 8:725–730

    Article  PubMed  CAS  Google Scholar 

  • Sharin VG, Mujoo K, Kots AY, Martin E, Murad F, Sharina IG (2010) Nitric oxide receptor soluble Guanylyl cyclase undergoes splicing regulation in differentiating human embryonic cells. Stem Cells Dev 20:1287–1293

    Google Scholar 

  • Spallotta F, Rosati J, Straino S, Nanni S, Grasselli A, Ambrosino V, Rotili D, Valente S, Farsetti A, Mai A, Capogrossi MC, Gaetano C, Illi B (2010) Nitric oxide determines mesodermic differentiation of mouse embryonic stem cells by activating class IIa histone deacetylases: potential therapeutic implications in a mouse model of hindlimb ischemia. Stem Cells 28:431–442

    PubMed  CAS  Google Scholar 

  • Tapia-Limonchi R, Mora-Castilla. S, Cahuana GM, Hitos AB, Martin F, Soria B, Bedoya FJ, Tejedo JR (2011) Gene regulation of mouse embryonic stem cells by low nitric oxide (submitted)

    Google Scholar 

  • Tejedo JR, Tapia-Limonchi R, Mora-Castilla S, Cahuana GM, Hmadcha A, Martin F, Bedoya FJ, Soria B (2010) Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival. Cell Death Dis 1:e80

    Article  PubMed  CAS  Google Scholar 

  • Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S, Hussain P, Vecoli C, Paolocci N, Ambs S, Colton CA, Harris CC, Roberts DD, Wink DA (2008) The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med 45:18–31

    Article  PubMed  CAS  Google Scholar 

  • Tsutsui M, Shimokawa H, Morishita T, Nakashima Y, Yanagihara N (2006) Development of genetically engineered mice lacking all three nitric oxide synthases. J Pharmacol Sci 102:147–154

    Article  PubMed  CAS  Google Scholar 

  • Yamane T, Dylla SJ, Muijtjens M, Weissman IL (2005) Enforced Bcl-2 expression overrides serum and feeder cell requirements for mouse embryonic stem cell self-renewal. Proc Natl Acad Sci USA 102:3312–3317

    Article  PubMed  CAS  Google Scholar 

  • Zhao T, Xu Y (2010) p53 and stem cells: new developments and new concerns. Trends Cell Biol 20:170–175

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Junta de Andalucía (CTS576 and PI-0105/2010) to FJ. Bedoya and from Consejería de Salud-Junta de Andalucía (PI-0723/2010) and Instituto de Salud Carlos III (CIBERDEM) to J.R. Tejedo.

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Authors and Affiliations

  1. Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University Pablo de Olavide, CIBERDEM, Seville, 41092, Spain

    Juan R. Tejedo, Gladys M. Cahuana, Francisco J. Bedoya & Rafael Tapia-Limonchi

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  1. Juan R. Tejedo
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  2. Gladys M. Cahuana
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  3. Francisco J. Bedoya
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  4. Rafael Tapia-Limonchi
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Corresponding author

Correspondence to Juan R. Tejedo .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Tejedo, J.R., Cahuana, G.M., Bedoya, F.J., Tapia-Limonchi, R. (2012). Embryonic Stem Cells: The Role of Nitric Oxide in Regulating Cell Differentiation, Self-Renewal, and Apoptosis. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells,Volume 3. Stem Cells and Cancer Stem Cells, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2415-0_36

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