Non-muscle myosin II regulates survival threshold of pluripotent stem cells.
Human pluripotent stem (hPS) cells such as human embryonic stem (hES) and induced pluripotent stem (hiPS) cells are vulnerable under single cell conditions, which hampers practical applications; yet, the mechanisms underlying this cell death remain elusive. In this paper, we demonstrate that treatment with a specific inhibitor of non-muscle myosin II (NMII), blebbistatin, enhances the survival of hPS cells under clonal density and suspension conditions, and, in combination with a synthetic matrix, supports a fully defined environment for self-renewal. Consistent with this, genetically engineered mouse embryonic stem cells lacking an isoform of NMII heavy chain (NMHCII), or hES cells expressing a short hairpin RNA to knock down NMHCII, show greater viability than controls. Moreover, NMII inhibition increases the expression of self-renewal regulators Oct3/4 and Nanog, suggesting a mechanistic connection between NMII and self-renewal. These results underscore the importance of the molecular motor, NMII, as a novel target for chemically engineering the survival and self-renewal of hPS cells.
Walker
Andrea
A
Department of Biochemistry, University of California, Riverside, Riverside, California 29521, USA.
Su
Hua
H
Conti
Mary Anne
MA
Harb
Nicole
N
Adelstein
Robert S
RS
Sato
Noboru
N
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007621:Karyotyping; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
D006576:Heterocyclic Compounds, 4 or More Rings; D034741:RNA, Small Interfering; C472645:blebbistatin; D024462:Myosin Type II