title: The abbreviated pluripotent cell cycle.
abstract: Human embryonic stem cells (hESCs) and induced pluripotent stem cells proliferate rapidly and divide symmetrically producing equivalent progeny cells. In contrast, lineage committed cells acquire an extended symmetrical cell cycle. Self-renewal of tissue-specific stem cells is sustained by asymmetric cell division where one progeny cell remains a progenitor while the partner progeny cell exits the cell cycle and differentiates. There are three principal contexts for considering the operation and regulation of the pluripotent cell cycle: temporal, regulatory, and structural. The primary temporal context that the pluripotent self-renewal cell cycle of hESCs is a short G1 period without reducing periods of time allocated to S phase, G2, and mitosis. The rules that govern proliferation in hESCs remain to be comprehensively established. However, several lines of evidence suggest a key role for the naïve transcriptome of hESCs, which is competent to stringently regulate the embryonic stem cell (ESC) cell cycle. This supports the requirements of pluripotent cells to self-propagate while suppressing expression of genes that confer lineage commitment and/or tissue specificity. However, for the first time, we consider unique dimensions to the architectural organization and assembly of regulatory machinery for gene expression in nuclear microenviornments that define parameters of pluripotency. From both fundamental biological and clinical perspectives, understanding control of the abbreviated ESC cycle can provide options to coordinate control of proliferation versus differentiation. Wound healing, tissue engineering, and cell-based therapy to mitigate developmental aberrations illustrate applications that benefit from knowledge of the biology of the pluripotent cell cycle.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kapinas
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grandy
authors.forename: Prachi
authors.initials: P
authors.lastname: Ghule
authors.forename: Ricardo
authors.initials: R
authors.lastname: Medina
authors.forename: Klaus
authors.initials: K
authors.lastname: Becker
authors.forename: Arthur
authors.initials: A
authors.lastname: Pardee
authors.forename: Sayyed K
authors.initials: SK
authors.lastname: Zaidi
authors.forename: Jane
authors.initials: J
authors.lastname: Lian
authors.forename: Janet
authors.initials: J
authors.lastname: Stein
authors.forename: Andre
authors.initials: A
authors.lastname: van Wijnen
authors.forename: Gary
authors.initials: G
authors.lastname: Stein
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D016259:Genes, myc / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D006657:Histones; D035683:MicroRNAs