作者: Peter D. Tonge , Peter W. Andrews
DOI: 10.1016/J.DIFF.2010.04.001
关键词: Cell biology 、 Retinoic acid 、 Biology 、 Neurogenesis 、 Stem cell 、 Embryonic stem cell 、 Cellular differentiation 、 SOX2 、 P19 cell 、 Induced pluripotent stem cell
摘要: Differentiation of human embryonic stem (ES) cells and embryonal carcinoma (EC) provides an in vitro model to study the process neuronal differentiation. Retinoic acid (RA) is frequently used promote neural differentiation pluripotent under a wide variety culture conditions. Through systematic comparison conditions we demonstrate that RA induced ES EC requires prolonged exposure intercellular communication mediated by high cell density. These parameters are necessary for up-regulation gene expression (SOX2, PAX6 NeuroD1) eventual appearance neurons. Forced over-expression neither SOX2 nor NEUROD1 was sufficient overcome density dependency Furthermore, inhibition GSK3beta activity blocked ability direct along lineage, suggesting role appropriately regulated WNT signalling. data indicate lines not autonomous program but comprises multi-staged input.