Robust Enhancement of Neural Differentiation from Human ES and iPS Cells Regardless of their Innate Difference in Differentiation Propensity
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Our analyses of three human induced pluripotent stem cell (hiPSC) and six human embryonic stem cell (hESC) lines showed marked variability in differentiation potential into specific lineages, which often hampers their differentiation into specific cell types or cell lineages of interest. Simultaneous inhibition of both Activin/Nodal and BMP pathways with small molecules, SB431542 and dorsomorphin (DM), respectively, promoted significant neural differentiation from all human pluripotent stem cell (hPSC) lines tested, regardless of their differentiation propensity. On the contrary, differentiation into other cell lineages and the number of undifferentiated cells were significantly reduced after differentiation by the dual inhibition. These results demonstrate that innate differentiation propensity of hPSCs could be overcome, at least in part, by modulation of intracellular signaling pathways, resulting in efficient generation of desirable cell types, such as neural cells.
KeywordsPluripotent stem cell Differentiation propensity Neural induction Cell signaling Small molecule
This research was supported by grants (code: SC1110, SC4140 and SC5170) from the Stem Cell Research Center of the 21th Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea.