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Reversine Increases the Plasticity of Lineage-committed Cells toward Neuroectodermal Lineage

Authors
Lee, EKBae, GUYou, JSLee, JCJeon, YJPark, JWPark, JHAhn, SHKim, YKChoi, WSKang, JSHan, GHan, JW
Issue Date
Jan-2009
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.284, no.5, pp 2891 - 2901
Pages
11
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume
284
Number
5
Start Page
2891
End Page
2901
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/148119
DOI
10.1074/jbc.M804055200
ISSN
0021-9258
1083-351X
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 re
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