Reversine increases the plasticity of lineage-committed cells toward neuroectodermal lineage

Kyung Lee Eun, Gyu Un Bae, Soo You Jueng, Cheol Lee Jae, Jee Jeon Yae, Woo Park Jong, Hyun Park Jae, Hoon Ahn Seong, Kee Kim Yong, Soo Choi Wahn, Jong Sun Kang, Gyoonhee Han, Jeung Whan Han

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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.

Original languageEnglish
Pages (from-to)2891-2901
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number5
DOIs
Publication statusPublished - 2009 Jan 30

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Eun, K. L., Bae, G. U., Jueng, S. Y., Jae, C. L., Yae, J. J., Jong, W. P., Jae, H. P., Seong, H. A., Yong, K. K., Wahn, S. C., Kang, J. S., Han, G., & Han, J. W. (2009). Reversine increases the plasticity of lineage-committed cells toward neuroectodermal lineage. Journal of Biological Chemistry, 284(5), 2891-2901. https://doi.org/10.1074/jbc.M804055200