title: Formula G1: Cell cycle in the driver's seat of stem cell fate determination.
abstract: Cell cycle dynamics has emerged as a key regulator of stem cell fate decisions. In particular, differentiation decisions are associated with the G1 phase, and recent evidence suggests that self-renewal is actively regulated outside of G1. The mechanisms underlying these phenomena are largely unknown, but direct control of gene regulatory programs by the cell cycle machinery is heavily implicated. A recent study sheds important mechanistic insight by demonstrating that in human embryonic stem cells (hESCs) the Cyclin-dependent kinase CDK2 controls a wide-spread epigenetic program that drives transcription at differentiation-related gene promoters specifically in G1. Here, we discuss this finding and explore whether similar mechanisms are likely to function in multipotent stem cells. The implications of this discovery toward our understanding of stem cell-related disease are discussed, and we postulate novel mechanisms that position the cell cycle as a regulator of cell fate gene networks at epigenetic, transcriptional and post-transcriptional levels.
authors: Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Faculty of Graduate and Postdoctoral Studies, Ottawa, ON, Canada.
authors: Lisa M
authors: LM
authors: Julian
authors: Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Faculty of Graduate and Postdoctoral Studies, Ottawa, ON, Canada.
authors: Richard L
authors: RL
authors: Carpenedo
authors: Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Faculty of Graduate and Postdoctoral Studies, Ottawa, ON, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
authors: Janet L Manias
authors: JL
authors: Rothberg
authors: Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.|Faculty of Graduate and Postdoctoral Studies, Ottawa, ON, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.|Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.|Ottawa Institute of Systems Biology, Ottawa, Ontario, Canada.
authors: William L
authors: WL
authors: Stanford
mesh_terms: D002454:Cell Differentiation; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D044127:Epigenesis, Genetic; D016193:G1 Phase / Q000235:genetics*; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D062085:RNA, Long Noncoding; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051785:Smad Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: G1 phase; bivalent promoter; cell cycle; cell fate; differentiation; pluripotency