123 M.A. Hayat (ed.), Stem Cells and Cancer Stem Cells, Volume 8, DOI 10.1007/978-94-007-4798-2_12, © Springer Science+Business Media Dordrecht 2012 12 Abstract Embryonic stem (ES) cells have two defining properties: self-renewal and pluripotency, and these make them a promising source for cell transplantation therapies. Oct4, Nanog, and Sox2 are the main transcription factors in regu- lating ES cell pluripotency. These key factors have also been identified that form an intrinsic core-regulatory circuit that maintains ES cells in the pluripotent state in vitro. The precise mechanism of how these processes are regulated remains largely unknown. Thus investigation of the molecular and cellular mechanisms of stem cell self-renewal and pluripotency provide the necessary tools to harness the regenerative potential of ES cells for therapeutic purposes. Recently, we have showed that natriuretic pep- tide receptor A (NPR-A), a specific receptor for atrial and brain natriuretic peptide (ANP and BNP), is expressed in preimplantation embryos and in ES cells, and is functional in ES cells. In this chapter, we will provide an overview on the importance of identifying the expression and function of NPR-A in maintaining ES cell characteristics. Introduction Embryonic stem (ES) cells are derived from inner cell mass (ICM) of the blastocysts (Evans and Kaufman 1981). They can undergo unlimited self-renewal and characterized by their potential Regulation of Self-Renewal and Pluripotency of Embryonic Stem Cells: Role of Natriuretic Peptide Receptor A Essam M. Abdelalim and Ikuo Tooyama E.M. Abdelalim (*) Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-Cho, Otsu, Shiga 520-2192, Japan e-mail: essam_abdelalim@yahoo.com I. Tooyama Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan Contents Introduction ............................................................ 123 Expression of NPR-A in Pluripotent ES Cells and Pre-implantation Embryos ................... 124 Role of NPR-A in ES Cell Proliferation ............... 125 Role of NPR-A in ES Cell Pluripotency ............... 126 NPR-A Ligands Enhance ES Cell Self-Renewal ............................................. 127 PI3K is Involved in NPR-A Functions in ES Cells ............................................. 128 Differentiation of NPR-A-Deficient ES Cells ....... 128 References ............................................................... 130