The molecular mechanisms that regulate the proliferation and differentiation of induced pluripotent stem (iPS) cells are of
great interest. However, whether stimulation with nicotine enhances the proliferation and differentiation of iPS cells has not been investigated.
In the present study, western blot analysis revealed that the α4-nAchR and α7-nAchR are expressed in mouse iPS cells. Mouse iPS
cells were treated with nicotine for 24 h under feeder-free conditions. Mouse iPS cells were guided to differentiate into mesodermal progenitor
cells on type IV collagen (Col IV)-coated dishes in differentiation medium. Mouse iPS cells were guided to differentiate into neural
progenitor cells by embryoid body (EB) formation on ultra-low-attachment dishes. After 4 days of growth, all-trans retinoic acid
(ATRA; 1 μM) or nicotine (300 nM) was added to the EB cultures and maintained for additional 4 days and plated onto fibronectincoated
plates. A BrdU incorporation assay showed that treatment with 300 nM nicotine significantly increased the DNA synthesis of
mouse iPS cells or mouse iPS cell-derived mesodermal progenitor cells. This effect was significantly inhibited by pretreatment with an
α4-nAchR antagonist, an α7-nAchR antagonist, or a CaMKII inhibitor. The differentiation potential of mouse iPS cells into mesodermal
progenitor cells or neural progenitor cells was not affected by the nicotine treatment. The present study indicates that stimulation of the
α4-nAchR and α7-nAchR may lead to a significant increase in the proliferation of mouse iPS cells or mouse iPS cell-derived mesodermal
progenitor cells through the CaMKII signaling pathway.
Keywords: Nicotine, nicotinic acetylcholine receptor, DNA synthesis, Ca2+/calmodulin-dependent protein kinase, induced pluripotent stem cells, mesodermal progenitor cells, Flk-1, neural progenitor cells, nestin, βIII-tubulin
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