Reversine increases the plasticity of lineage-committed mammalian cells.
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.
Chen
Shuibing
S
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Takanashi
Shinichi
S
Zhang
Qisheng
Q
Xiong
Wen
W
Zhu
Shoutian
S
Peters
Eric C
EC
Ding
Sheng
S
Schultz
Peter G
PG
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects*; D006651:Histocytochemistry; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects*; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D009025:Morpholines; D011687:Purines; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine