Melatonin improves reprogramming efficiency and proliferation of bovine-induced pluripotent stem cells.

Melatonin can modulate neural stem cell ( NSC) functions such as proliferation and differentiation into NSC-derived pluripotent stem cells (N- iPS) in brain tissue, but the effect and mechanism underlying this are unclear. Thus, we studied how primary cultured bovine NSCs isolated from the retinal neural layer could transform into N- iPS cell. NSCs were exposed to 0.01, 0.1, 1, 10, or 100 μ m melatonin, and cell viability studies indicated that 10 μ m melatonin can significantly increase cell viability and promote cell proliferation in NSCs in vitro. Thus, 10 μ m melatonin was used to study miR-302/367-mediated cell reprogramming of NSCs. We noted that this concentration of melatonin increased reprogramming efficiency of N- iPS cell generation from primary cultured bovine NSCs and that this was mediated by downregulation of apoptosis-related genes p53 and p21. Then, N- iPS cells were treated with 1, 10, 100, or 500 μ m melatonin, and N- iPS (M-N- iPS) cell proliferation was measured. We noted that 100 μ m melatonin increased proliferation of N- iPS cells via increased phosphorylation of intracellular ERK1/2 via activation of its pathway in M-N- iPS via melatonin receptors 1 ( MT1). Finally, we verified that N- iPS cells and M-N- iPS cells are similar to typical embryonic stem cells including the expression of pluripotency markers (Oct4 and Nanog), the ability to form teratomas in vivo , and the capacity to differentiate into all three embryonic germ layers. [ABSTRACT FROM AUTHOR]