期刊
CELL STEM CELL
卷 7, 期 1, 页码 90-100出版社
CELL PRESS
DOI: 10.1016/j.stem.2010.04.017
关键词
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资金
- National Institutes of Neurological Diseases and Stroke [NS045926]
- National Institute of Child Health and Human Development [P30 HD03352]
- Ministry of Science and Technology, China [2006CB94700, 2006AA02A101]
- Shanghai Municipality [06dj14001]
- NIH [RR00167, RR15459, RR020141]
The transcriptional regulation of neuroectoderm (NE) specification is unknown. Here we show that Pax6 is uniformly expressed in early NE cells of human fetuses and those differentiated from human embryonic stem cells (hESCs). This is in contrast to the later expression of Pax6 in restricted mouse brain regions. Knockdown of Pax6 blocks NE specification from hESCs. Overexpression of either Pax6a or Pax6b, but not Pax6 Delta PD, triggers hESC differentiation. However, only Pax6a converts hESCs to NE. In contrast, neither loss nor gain of function of Pax6 affects mouse NE specification. Both Pax6a and Pax6b bind to pluripotent gene promoters but only Pax6a binds to NE genes during human NE specification. These findings indicate that Pax6 is a transcriptional determinant of the human NE and suggest that Pax6a and Pax6b coordinate with each other in determining the transition from pluripotency to the NE fate in human by differentially targeting pluripotent and NE genes.
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