title: Non-muscle myosin II regulates survival threshold of pluripotent stem cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California 29521, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Walker
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Conti
authors.forename: Nicole
authors.initials: N
authors.lastname: Harb
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.forename: Noboru
authors.initials: N
authors.lastname: Sato
mesh_terms: 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
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D034741:RNA, Small Interfering; C472645:blebbistatin; D024462:Myosin Type II