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tsa hdac br Integrin Expression in Human Stem Cells Integrin
Integrin Expression in Human Stem Cells
Integrin expression in human embryonic stem tsa hdac and selected adult stem cell types is summarised in Table 2. We define here the known expression profiles of integrins on human stem cells of four different types: embryonic, mesenchymal, haematopoietic and neural.
In an experiment investigating differentiation of hESC towards definitive endoderm, Wong and colleagues show up-regulation of the vitronectin/fibronectin specific integrin subunits αV, α5, β3, β5 and β6 and a down regulation of the laminin specific subunits α3, α6 and β4 (Wong et al., 2010). This work suggests there may be a requirement to alter ECM constitution in order to effectively differentiate hESC towards the intended lineage and mature adult cell phenotype, in this case definitive endoderm. Similarly, the oligodendrocyte progenitor cells produced by Geron from human embryonic stem cells for phase I clinical trials for treatment of acute spinal cord injury (Briefing, 2010) were grown on Matrigel for much of the differentiation process before transfer to laminin for terminal differentiation (Nistor et al., 2005; Keirstead et al., 2005). In another example, van Laake and colleagues have shown changes in integrin expression in hESC during differentiation to cardiomyocytes in mouse transplantation experiments (van Laake et al., 2010). Here, changes in the expression of different integrin receptors for laminin were observed (α3 up regulated and α6 down regulated) during in vivo maturation of hESC derived cardiomyocytes indicating different laminin isotypes may play a role while the fibronectin/vitronectin specific subunits αV and α5 were down regulated. Pruszak et al. have similarly shown changes in integrin expression during different stages of neural precursor differentiation and a down regulation of β1 (Pruszak et al., 2009). These examples highlight that lineage specific differentiation of hESC might be better facilitated by altering the ECM makeup to include or exclude certain ECM molecules and develop a mature, differentiated phenotype.
Given the evidence presented so far regarding effects of integrin mediated cell responses, it should be apparent that tools to investigate cell-ECM interactions are paramount for the use of hESC and adult stem cell types in clinical applications. Tools for defining ECM matrices in vitro are of critical importance given that it has been shown certain cell types only express some integrins in tissue culture environments. For example α5β1, a fibronectin receptor is only expressed in keratinocytes in vivo during disease phenotypes or wound healing and this is an expression also observed in vitro due likely to stress of the tissue culture environment (Watt, 2002).
Conclusion/Future Directions
Acknowledgments
Introduction
Human embryonic stem cells (hESC) are derived from the inner cell mass of an early embryo and possess a unique developmental potential. They are defined as pluripotent because of their capacity to differentiate into all cell lineages present in embryonic tissue. In addition, hESC can self-renew and be cultured indefinitely in vitro. Because hESC have been shown to undergo robust in vitro differentiation, these cells may be considered a powerful tool to explore different events affecting cardiac cells (Lev et al., 2005), including molecular pathogenesis and drug and toxicology testing (Steel et al., 2009; Reppel et al., 2007). The development of induced pluripotent stem cells (iPS) expands these possibilities further, since it is now possible to study cardiomyocytes derived from reprogrammed somatic cells of patients with cardiac disease (Yokoo et al., 2009; Zhang et al., 2009).
Coxsackieviruses B (CVB), which include 6 serotypes, are human enteroviruses belonging to the Picornaviridae family (Pallansch and Roos, 2001). Together with CVA9 and the echoviruses (EV), CVB are currently classified as type B Enteroviruses (Stanway et al., 2004), interacting with at least two receptor proteins present on the cytoplasmic membrane. All CVB, as well as some adenoviruses, recognize and enter the cell through the coxsackievirus-adenovirus receptor (CAR), which is a 46-kDa protein belonging to the immunoglobulin supergene family (Bergelson et al., 1997). Although viral uncoating is initiated only by CAR interactions (Milstone et al., 2005), some CVB interact with an additional 70-kDa molecule known as the decay-accelerating factor (DAF, also known as CD55), which is a surface-expressed complement regulatory protein (Shafren et al., 1995). With the exception of CVB6, all CVB serotypes are expected to produce similar diseases (Pallansch and Roos, 2001); nevertheless, most experimental studies have been performed with CVB3 because some viral variants may induce myocarditis in animal models (Tracy and Gauntt, 2008). CVB1 was the predominant enterovirus circulating in the US during 2007 (Anon, 2008), and viruses derived from an infectious clone (Iizuka et al., 1991) have been used in several studies (Rinehart et al., 1997; Zhong et al., 2008).