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Madison, WI, United States

Zhang X.,Waisman Center and the ll Institute | Huang C.T.,Waisman Center and the ll Institute | Chen J.,Fudan University | Pankratz M.T.,Waisman Center and the ll Institute | And 12 more authors.
Cell Stem Cell | Year: 2010

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 restrictedmouse brain regions. Knockdown of Pax6 blocks NE specification from hESCs. Overexpression of either Pax6a or Pax6b, but not Pax66PD, triggers hESC differentiation. However, only Pax6 Δ 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. © 2010 Elsevier Inc.

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