Embryonic stem cells （ESCs） can undergo unlimited self-renewal and maintain pluripotency to differen- tiate into any cell type of the three germ layers. Extensive studies have shown ESC identity is regulated by tran...Embryonic stem cells （ESCs） can undergo unlimited self-renewal and maintain pluripotency to differen- tiate into any cell type of the three germ layers. Extensive studies have shown ESC identity is regulated by transcription factors, epigenetic regulators and multiple signal transduction pathways. However, the kinase regulation of pluripotency is not well understood. Here we show that the serine/threonine kinase PlM2, which is highly expressed in ESCs but not in somatic cells, functions as a crucial stemness regulator in ESCs. Knockout of Pim2 inhibits the self-renewal and differentiation capability of ESCs. Mechanistic studies identified that PIM2 can directly phosphorylate 4E-BP1, leading to release of elF4E which facili- tates the translation of pluripotent genes in ESCs. Our study highlights a novel kinase cascade pathway for ESC identity maintenance.展开更多
基金supported by the National Basic Research Program of China (2013CB966901)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01040108)The National Thousand of Talents Program to T.Z., and the National Natural Science Foundation of China (31570995, 31621004) to T.Z. and (31400831) to J.C.
文摘Embryonic stem cells （ESCs） can undergo unlimited self-renewal and maintain pluripotency to differen- tiate into any cell type of the three germ layers. Extensive studies have shown ESC identity is regulated by transcription factors, epigenetic regulators and multiple signal transduction pathways. However, the kinase regulation of pluripotency is not well understood. Here we show that the serine/threonine kinase PlM2, which is highly expressed in ESCs but not in somatic cells, functions as a crucial stemness regulator in ESCs. Knockout of Pim2 inhibits the self-renewal and differentiation capability of ESCs. Mechanistic studies identified that PIM2 can directly phosphorylate 4E-BP1, leading to release of elF4E which facili- tates the translation of pluripotent genes in ESCs. Our study highlights a novel kinase cascade pathway for ESC identity maintenance.
