Robust enhancement of neural differentiation from human ES and iPS cells regardless of their innate difference in differentiation propensity.
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.
Kim
Dae-Sung
DS
Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, [corrected] Seoul, 120-752, Korea.
Lee
Jae Souk
JS
Leem
Joong Woo
JW
Huh
Yong Jun
YJ
Kim
Ji Young
JY
Kim
Han-Soo
HS
Park
In-Hyun
IH
Daley
George Q
GQ
Hwang
Dong-Youn
DY
Kim
Dong-Wook
DW
D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology