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Maintenance of Embryonic Stem Cell Pluripotency by Nanog-Mediated Dedifferentiation of Committed Mesoderm Progenitors

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

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Embryonic stem (ES) cells 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 ES cell pluripotency are, however, poorly understood. Here, we characterize a population of early mesoderm-committed (EM) progenitors that is generated from mouse ES cells by bone morphogenetic protein (BMP) stimulation. We further show that EM progenitors are actively dedifferentiated to ES cells by the action of Nanog, which, in turn, is directly up-regulated in EM progenitors by the combined action of leukemia inhibitory factor (LIF) and the early mesoderm transcription factor T/Brachyury. Finally, we demonstrate that this negative feedback mechanism contributes to the maintenance of ES cell pluripotency. These findings uncover specific roles of LIF, Nanog, and BMP in the self-renewal of ES cells and provide novel insights into the cellular bases of ES cell pluripotency.

Original languageEnglish (US)
Title of host publicationStem Cell Biology and Regenerative Medicine
PublisherSpringer Nature
Pages37-53
Number of pages17
DOIs
StatePublished - 2009
Externally publishedYes

Publication series

NameStem Cell Biology and Regenerative Medicine
VolumePart F4844
ISSN (Print)2196-8985
ISSN (Electronic)2196-8993

Bibliographical note

Publisher Copyright:
© Humana Press, a part of Springer Science+Business Media, LLC, a part of Springer Science+Business Media, LLC 2009.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Leukemia inhibitory factor
  • Mesoderm differentiation
  • Pluripotency
  • Self-renewal
  • T (Brachyury)

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