title: Human pancreatic β-cell G1/S molecule cell cycle atlas.
abstract: Expansion of pancreatic β-cells is a key goal of diabetes research, yet induction of adult human β-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human β-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control molecules in the human β-cell. This atlas reveals that the majority of these molecules, previously known to be present in islets, are actually present in the β-cell. More importantly, and in contrast to anticipated results, the human β-cell G1/S atlas reveals that almost all of the critical G1/S cell cycle control molecules are located in the cytoplasm of the quiescent human β-cell. Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human β-cell proliferation are present in the nuclear compartment. This observation may provide an explanation for the refractoriness of human β-cells to proliferation. Thus, in addition to known obstacles to human β-cell proliferation, restriction of G1/S molecules to the cytoplasm of the human β-cell represents an unanticipated obstacle to therapeutic human β-cell expansion.
authors.affiliation: Division of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. nmt2@pitt.edu
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Fiaschi-Taesch
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Kleinberger
authors.forename: Fatimah G
authors.initials: FG
authors.lastname: Salim
authors.forename: Ronnie
authors.initials: R
authors.lastname: Troxell
authors.forename: Rachel
authors.initials: R
authors.lastname: Wills
authors.forename: Mansoor
authors.initials: M
authors.lastname: Tanwir
authors.forename: Gabriella
authors.initials: G
authors.lastname: Casinelli
authors.forename: Amy E
authors.initials: AE
authors.lastname: Cox
authors.forename: Karen K
authors.initials: KK
authors.lastname: Takane
authors.forename: Donald K
authors.initials: DK
authors.lastname: Scott
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D002453:Cell Cycle / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002648:Child; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D013347:Subcellular Fractions
chemical_list: D016213:Cyclins; D018844:Cyclin-Dependent Kinases