Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification

Nature Clinical Practice. Cardiovascular Medicine
Atsushi SuzukiJuan Carlos Izpisua Belmonte

Abstract

Embryonic stem cells (ESCs) can be propagated indefinitely in culture, while retaining the ability to differentiate into any cell type in the organism. The molecular and cellular mechanisms underlying ESC pluripotency are, however, poorly understood. We characterize a population of early mesoderm-specified (EM) progenitors that is generated from mouse ESCs by bone morphogenetic protein stimulation. We further show that pluripotent ESCs are actively regenerated from EM progenitors by the action of the divergent homeodomain-containing protein Nanog, which, in turn, is upregulated in EM progenitors by the combined action of leukemia inhibitory factor and the early mesoderm transcription factor T/Brachyury. These findings uncover specific roles of leukemia inhibitory factor, Nanog, and bone morphogenetic protein in the self-renewal of ESCs and provide novel insights into the cellular bases of ESC pluripotency.

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Citations

Jun 1, 2008·Journal of Cardiovascular Translational Research·Randolph S Faustino, Andre Terzic
Dec 22, 2007·Nature·Ian ChambersAustin Smith
Jun 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Atsushi SuzukiJuan Carlos Izpisúa Belmonte
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