| Literature DB >> 16801560 |
Atsushi Suzuki1,2, Ángel Raya1,2,3, Yasuhiko Kawakami1, Masanobu Morita1,2, Takaaki Matsui1, Kinichi Nakashima4,5, Fred H Gage2,4, Concepción Rodríguez-Esteban1, Juan Carlos Izpisúa Belmonte6,2,3.
Abstract
ES cells represent a valuable model for investigating early embryo development and hold promise for future regenerative medicine strategies. The self-renewal of pluripotent mouse ES cells has been shown to require extrinsic stimulation by the bone morphogenetic protein (BMP) and leukemia inhibitory factor signaling pathways and the expression of the transcription factors Oct4 and Nanog. However, the network of interactions among extrinsic and intrinsic determinants of ES cell pluripotency is currently poorly understood. Here, we show that Nanog expression is up-regulated in mouse ES cells by the binding of T (Brachyury) and STAT3 to an enhancer element in the mouse Nanog gene. We further show that Nanog blocks BMP-induced mesoderm differentiation of ES cells by physically interacting with Smad1 and interfering with the recruitment of coactivators to the active Smad transcriptional complexes. Taken together, our findings illustrate the existence of ES cell-specific regulatory networks that underlie the maintenance of ES cell pluripotency and provide mechanistic insights into the role of Nanog in this process.Entities:
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Year: 2006 PMID： 16801560 PMCID： PMC1502451 DOI： 10.1073/pnas.0506945103
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205