Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells

Atsushi Suzuki, Ángel Raya, Yasuhiko Kawakami, Masanobu Morita, Takaaki Matsui, Kinichi Nakashima, Fred H. Gage, Concepción Rodríguez-Esteban, Juan Carlos Izpisúa Belmonte

Research output: Contribution to journalArticle

196 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10294-10299
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number27
DOIs
Publication statusPublished - Jul 4 2006

All Science Journal Classification (ASJC) codes

  • General

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