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doi: 10.1242/10.1242/dev.00476
1 Department of Cell Fate Modulation, Institute of Molecular Embryology and
Genetics, Kumamoto University, Kumamoto, 860-0811, Japan
2 Laboratory of Pluripotent Cell Studies, RIKEN Center for Developmental
Biology, Kobe, 650-0047, Japan
* Authors for correspondence: taga{at}kaiju.medic.kumamoto-u.ac.jp and kin{at}kaiju.medic.kumamoto-u.ac.jp
Accepted 10 March 2003
Oct3/4 plays a critical role in maintaining embryonic stem cell pluripotency. Regulatable transgene-mediated sustained Oct3/4 expression in ES cells cultured in serum-free LIF-deficient medium caused accelerated differentiation to neuroectoderm-like cells that expressed Sox2, Otx1 and Emx2 and subsequently differentiated into neurons. Neurogenesis of ES cells is promoted by SDIA (stromal cell-derived inducing activity), which accumulates on the PA6 stromal cell surface. Oct3/4 expression in ES cells was maintained by SDIA whereas without it expression was promptly downregulated. Suppression of Oct3/4 abolished neuronal differentiation even after stimulation by SDIA. In contrast, sustained upregulated Oct3/4 expression enhanced SDIA-mediated neurogenesis of ES cells. Therefore, Oct3/4 appears to promote neuroectoderm formation and subsequent neuronal differentiation from ES cells.
Key words: Oct3/4, SDIA, ES cells, Neurogenesis, LIF, Mouse
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