Profile of Galanin in Embryonic Stem Cells and Tissues

In the preimplantation mammalian embryo, cells of the inner cell mass can differentiate into any cell type present in the more mature embryo. As of 1981, in mice and 1998 in humans, it has been recognized that embryonic stem cells (ESCs) with a prolonged proliferative capacity can be derived from the inner cell mass in vitro (Evans and Kaufman 1981; Thomson, Itskovitz-Eldor et al. 1998). ESCs are pluripotent cells that can contribute to all tissues in vivo and to the three primary germ layers as well as extraembryonic tissues in vitro. Because pluripotency is maintained in these cells even after prolonged periods of culture, human ESCs have great therapeutic potential for tissue regeneration. Indeed, embryonic and adult stem cells (SCs) hold great promise for regenerative medicine, tissue repair, and gene therapy. Careful molecular characterization of embryonic pluripotency should help to optimize and scale up the in vitro production of ESCs for clinical applications. The mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. As compared with differentiated cell types, stem cells express a significantly higher number of genes (represented by expressed sequence tags) of unknown function. The properties that distinguish stem cells from other cells are largely unknown, and the identification of signals that regulate stem cell differentiation remains fundamental to our understanding of cellular diversity. Embryonic and adult stem cells have many similarities at the transcriptional level. The overlapping set of expressed gene products represents a molecular signature of stem cells (Bhattacharya, Miura et al. 2004; Assou, Le Carrour et al. 2007). A list of human and mouse genes involved in stemness has been generated (Assou, Le Carrour et al. 2007) and includes 92 stemness genes known to be expressed in mouse or human ESCs, e.g., OCT3/4, NANOG, Cripto/TDGFI, Cx43 and Galanin (Richards, Tan et al. 2004). Work in the field of embryogenesis has also contributed to our understanding of the function of these pluripotency-associated genes. The four most significantly overexpressed genes in undifferentiated embryonic tissues are Galanin, POU5FI, NANOG and DPPA4 (Zeng, Miura et al. 2004). In most studies, galanin has been highlighted as the most abundant transcript in ES culture as well as human and rodent embryonic tissues (Anisimov, Tarasov et al. 2002; Zeng, Miura et al. 2004). Both galanin and galanin receptors are expressed in ES cells, indicating a potential functional role for this protein (Tarasov, Tarasova et al. 2002). This chapter will be devoted to a description of the galanin expression profiles in embryonic tissues and stem cells as well as its possible functional role.