Hartman Institute for Therapeutic Organ Regeneration

Reversine increases the plasticity of lineage-committed mammalian cells.

TitleReversine increases the plasticity of lineage-committed mammalian cells.
Publication TypeJournal Article
Year of Publication2007
AuthorsChen S, Takanashi S, Zhang Q, Xiong W, Zhu S, Peters EC, Ding S, Schultz PG
JournalProc Natl Acad Sci U S A
Volume104
Issue25
Pagination10482-7
Date Published2007 Jun 19
ISSN0027-8424
Keywords3T3 Cells, Adipocytes, Animals, Cell Differentiation, Cell Line, Cell Lineage, Histocytochemistry, Humans, Mice, Molecular Structure, Morpholines, Myoblasts, Skeletal, Osteoblasts, Purines, Time Factors
Abstract

Previously, a small molecule, reversine, was identified that reverses lineage-committed murine myoblasts to a more primitive multipotent state. Here, we show that reversine can increase the plasticity of C2C12 myoblasts at the single-cell level and that reversine-treated cells gain the ability to differentiate into osteoblasts and adipocytes under lineage-specific inducing conditions. Moreover, reversine is active in multiple cell types, including 3T3E1 osteoblasts and human primary skeletal myoblasts. Biochemical and cellular experiments suggest that reversine functions as a dual inhibitor of nonmuscle myosin II heavy chain and MEK1, and that both activities are required for reversine's effect. Inhibition of MEK1 and nonmuscle myosin II heavy chain results in altered cell cycle and changes in histone acetylation status, but other factors also may contribute to the activity of reversine, including activation of the PI3K signaling pathway.

DOI10.1073/pnas.0704360104
Alternate JournalProc Natl Acad Sci U S A
PubMed ID17566101
PubMed Central IDPMC1965539
Grant ListR21 HD047452 / HD / NICHD NIH HHS / United States
R21HD47452 / HD / NICHD NIH HHS / United States

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