Knock down effects of Jak2/Tyk2 for the Maintenance and Differentiation of Mouse Embryonic Stem Cells

Abstract

The propagation of pluripotent mouse embryonic stem cells (mESCs) depends on signals transduced through LIF-dependent Jak/STAT pathway. Although several Jak isoforms (Jak1, Jak2 and Tyk2) were expressed in mESCs, functional role of each isoforms was not tested for the maintenance of stemness and differentiation of mESCs. In this study, we established two Jak2/Tyk2 knockdown cell lines (Jak2#5N and Jak2#16), in which expression of both Jak2 and Tyk2 was greatly reduced or completely abolished, respectively, using a retroviral Jak2 RNAi vector, and tested their effect for the maintenance of stemness and differentiation. Our data indicate that Jak2/Tyk2 expression per se is not sufficient to the propagation of mESCs. During differentiation in vitro, however, three germ layer markers were expressed at early days of differentiation than control mESCs, and the definitive erythroid marker, but not the primitive one, was dramatically decreased. In addition, as revealed by cDNA microarray, lots of genes expressed in ectodermal and mesodermal lineage cells were also changed in their expression by the Jak2/Tyk2 knockdown.