TY - JOUR
T1 - Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification
AU - Suzuki, Atsushi
AU - Raya, Ángel
AU - Kawakami, Yasuhiko
AU - Morita, Masanobu
AU - Matsui, Takaaki
AU - Nakashima, Kinichi
AU - Gage, Fred H.
AU - Rodríguez-Esteban, Concepcín
AU - Izpiśa Belmonte, Juan Carlos
PY - 2006/3/1
Y1 - 2006/3/1
N2 - 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.
AB - 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.
KW - Embryonic stem cell
KW - Mesoderm specification
KW - Nanog
KW - Pluripotency
KW - Regenerative medicine
UR - http://www.scopus.com/inward/record.url?scp=33644632992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644632992&partnerID=8YFLogxK
U2 - 10.1038/ncpcardio0442
DO - 10.1038/ncpcardio0442
M3 - Article
C2 - 16501617
AN - SCOPUS:33644632992
SN - 1743-4297
VL - 3
JO - Nature Clinical Practice Cardiovascular Medicine
JF - Nature Clinical Practice Cardiovascular Medicine
IS - SUPPL. 1
ER -
