title: Melatonin improves reprogramming efficiency and proliferation of bovine-induced pluripotent stem cells.
abstract: 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 μm melatonin, and cell viability studies indicated that 10 μm melatonin can significantly increase cell viability and promote cell proliferation in NSCs in vitro. Thus, 10 μm 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 μm melatonin, and N-iPS (M-N-iPS) cell proliferation was measured. We noted that 100 μm 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.
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Bai
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Xiangchen
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.|College of Wildlife Resources, Northeast Forestry University, Harbin, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.|College of Wildlife Resources, Northeast Forestry University, Harbin, China.
authors.forename: Ziao
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.|Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Hu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.|Department of Food Science and Engineering, Liaoning Medical University, Jinzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.|Department of Bioscience, Bengbu Medical College, Bengbu, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Guan
authors.affiliation: Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D065150:Cellular Reprogramming / Q000187:drug effects*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D008550:Melatonin
keywords: cell proliferation; cell reprogramming; induced pluripotent stem cells; melatonin; neural stem cells