title: A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation.
abstract: Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138 schetty@mcb.harvard.edu dmelton@harvard.edu.
authors.forename: Sundari
authors.initials: S
authors.lastname: Chetty
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138.
authors.forename: Elise N
authors.initials: EN
authors.lastname: Engquist
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138.
authors.forename: Elie
authors.initials: E
authors.lastname: Mehanna
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138.
authors.forename: Kathy O
authors.initials: KO
authors.lastname: Lui
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138 Broad Institute of MIT and Harvard, Cambridge, MA 02142.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Tsankov
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA 02138 Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138 schetty@mcb.harvard.edu dmelton@harvard.edu.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D016392:Proto-Oncogene Proteins pp60(c-src); D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase / Q000187:drug effects
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D016160:Retinoblastoma Protein; D016392:Proto-Oncogene Proteins pp60(c-src)