title: Reversine increases the plasticity of lineage-committed cells toward neuroectodermal lineage.
abstract: Functional dedifferentiation of lineage-committed cells toward pluripotency may have a great potential in regenerative medicine. Reversine has been shown to induce dedifferentiation of multiple terminally differentiated mesodermal origin cells, which are capable of being directed to differentiate into other cell types within mesodermal lineages. However, the possibilities of these cells to give rise to other lineages have not been examined. Here we show that large scale gene expression profiling of reversine-treated C2C12 myoblasts identifies a subset of up-regulated genes involved in specification of neuroectodermal as well as mesodermal lineages. Reversine treatment leads to up-regulation of priming genes of neuroectodermal lineages, such as Ngn2, Nts, Irx3, Pax7, Hes1, and Hes6, through active histone modifications in the promoter regions of these genes. Additionally, reversine increases the expression of markers for other cell types of mesodermal lineages, Ogn and apoE, via inducing active histone modifications, while down-regulating the myogenic basic helix-loop-helix factor, MyoD, via repressive histone modifications. Consistent with up-regulation of these genes, reversine-treated C2C12 myoblasts redifferentiate into neural as well as mesodermal lineages, under appropriate stimuli. Taken together, these results indicate that reversine induces a multipotency of C2C12 myoblasts via inducing a specific combination of active histone modifications. Collectively, our findings provide a mechanistic rationale for the application of reversine to dedifferentiation of somatic cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Sungkyunkwan University, Suwon 440-746.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746.
authors.forename: Jueng Soo
authors.initials: JS
authors.lastname: You
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746.
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746.
authors.forename: Yae Jee
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Molecular and Life Sciences, Hanyang University, Ansan 426-791.
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: College of Medicine, Kwandong University, Gangneung 210-701.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: College of Medicine, Konkuk University, Chungju 380-701.
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Samsung Biomedical Research Institute, Sungkyunkwan University, Suwon 440-746.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Suwon 440-746. Electronic address: jhhan551@skku.edu.
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage; D017931:DNA Primers; D020869:Gene Expression Profiling; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine