Critical role of Rgs19 in mouse embryonic stem cell proliferation and differentiation

Mouse embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the ability to differentiate into the three germ layers required to form all embryonic tissues. These properties are maintained by both intrinsic and extrinsic factors. Many studies have contributed to the understanding of the molecular signal transduction required for pluripotency and controlled differentiation. Such an understanding is important in the potential application of stem cells to cell therapy for disease, and thus there is an interest in understanding the cell cycle regulation, pluripotency, and differentiation of ESCs. The regulator of G protein signaling (RGS) family consists of over 20 members. Rgs19, one such protein, specifically interacts with Gαi to enhance its GTPase activity. Growth factor receptors use Gi proteins for signal transduction, and Rgs19 may thus be involved in the regulation of cell proliferation. In a previous gain-of-function study, Rgs19 overexpression was found to enhance proliferation in various cell types. Our data demonstrate a role for Rgs19 in the regulation of ESC differentiation. Based on the presence of Rgs19 in ESCs, the morphological and molecular properties of wild-type and Rgs19 +/- ESCs during LIF withdrawal, in vitro differentiation, and teratoma formation were compared. Our findings provide insight for the first time into the mechanisms involved in Rgs19 regulation of mouse ESC proliferation and differentiation.