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.
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Suzuki, A. et al. (2009). Maintenance of Embryonic Stem Cell Pluripotency by Nanog-Mediated Dedifferentiation of Committed Mesoderm Progenitors. In: Rajasekhar, V.K., Vemuri, M.C. (eds) Regulatory Networks in Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press. https://doi.org/10.1007/978-1-60327-227-8_4
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DOI: https://doi.org/10.1007/978-1-60327-227-8_4
Publisher Name: Humana Press
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