Abstract
BackgroundIdentification of receptor mediated signaling pathways in embryonic stem (ES) cells is needed to facilitate strategies for cell replacement using ES cells. One large receptor family, largely uninvestigated in ES cells, is G protein coupled receptors (GPCRs). An important role for these receptors in embryonic development has been described, but little is known about GPCR expression in ES cells.Methodology/Principal FindingsWe have examined the expression profile of 343 different GPCRs in mouse ES cells demonstrating for the first time that a large number of GPCRs are expressed in undifferentiated and differentiating ES cells, and in many cases at high levels. To begin to define a role for GPCR signaling in ES cells, the impact of activating Gs-alpha, one of the major alpha subunits that couples to GPCRs, was investigated. Gs-alpha activation resulted in larger embryoid bodies (EBs), due, in part, to increased cell proliferation and prevented the time-related decline in expression of transcription factors important for maintaining ES cell pluripotency.Significance/ConclusionsThese studies suggest that Gs-alpha signaling contributes to ES cell proliferation and pluripotency and provide a framework for further investigation of GPCRs in ES cells.
Highlights
In embryonic stem (ES) cells, receptor mediated signaling pathways are important for maintaining pluripotency [1,2], a state characterized by the ability of ES cells to differentiate into cell types from all three germ layers [2,3]
To explore the expression profile of G protein coupled receptors (GPCRs) in ES cells, two main approaches were used, real time room temperature (RT)-PCR microarrays and data mining of expressed sequence tag (EST) libraries specific to ES cells
All of these receptors were expressed in our real time RT-PCR microarrays at one of the time points evaluated in our study
Summary
In embryonic stem (ES) cells, receptor mediated signaling pathways are important for maintaining pluripotency [1,2], a state characterized by the ability of ES cells to differentiate into cell types from all three germ layers [2,3]. Despite the importance of GPCRs in development, with the exception of the Frizzled receptors [17], the role of GPCRs in ES cell pluripotency and differentiation has received little attention [18]. Since GPCRs are readily targetable sites for small molecules, as evidenced by their role as drug targets in humans [9], characterization of GPCRs and related signaling molecules in ES cells may facilitate developing new approaches to ES cell differentiation. An important role for these receptors in embryonic development has been described, but little is known about GPCR expression in ES cells
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