Effect of leukemia inhibitory factor on embryonic stem cell differentiation: implications for supporting neuronal differentiation
Abstract
Aim: 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. Conclusion:
These results suggest that LIF plays a positive role during the differentiation of
ES cells into neuronal cells.
Keywords:
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. Conclusion:
These results suggest that LIF plays a positive role during the differentiation of
ES cells into neuronal cells.