Effect of leukemia inhibitory factor on embryonic stem cell differentiation: implications for supporting neuronal differentiation.
OBJECTIVE
Leukemia inhibitory factor (LIF), a pleiotropic cytokine, has been used extensively in the maintenance of mouse embryonic stem cell pluripotency. In this current work, we examined the effect of the LIF signaling pathway in embryonic stem (ES) cell differentiation to a neural fate.


METHODS
In the presence of LIF (1000 U/mL), the production of neuronal cells derived from embryoid bodies (EB) was tested under various culture conditions. Inhibition of the LIF pathway was examined with specific inhibitors. The effects of cell apoptosis and proliferation on neural differentiation were examined. ES cell differentiation into three-germ layers was compared.


RESULTS
Under various culture conditions, neuronal differentiation was increased in the presence of LIF. Blocking the LIF-activated STAT3 signaling pathway with specific inhibitors abolished the neuronal differentiation of ES cells, whereas inhibition of the LIF-activated MEK signaling pathway impaired the differentiation of ES cells toward a glial fate. LIF suppressed cell apoptosis and promoted cell proliferation during ES cell differentiation. LIF inhibited the differentiation of ES cells to both mesoderm and extraembryonic endoderm fates, but enhanced the determination of neural progenitors.


CONCLUSIONS
These results suggest that LIF plays a positive role during the differentiation of ES cells into neuronal cells.
He
Zhao
Z
Laboratory of Molecular and Cell Biology and Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
Li
Jing-jing
JJ
Zhen
Chang-hong
CH
Feng
Lin-ying
LY
Ding
Xiao-yan
XY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology*; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050796:STAT3 Transcription Factor; D020930:MAP Kinase Kinase Kinases