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

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

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)S114-S122
JournalNature Clinical Practice Cardiovascular Medicine
Issue numberSUPPL. 1
StatePublished - Mar 2006
Externally publishedYes


  • Embryonic stem cell
  • Mesoderm specification
  • Nanog
  • Pluripotency
  • Regenerative medicine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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