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Human pancreatic ?-cell G1/S molecule cell cycle atlas.

ABSTRACT: Expansion of pancreatic ?-cells is a key goal of diabetes research, yet induction of adult human ?-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human ?-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control molecules in the human ?-cell. This atlas reveals that the majority of these molecules, previously known to be present in islets, are actually present in the ?-cell. More importantly, and in contrast to anticipated results, the human ?-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 ?-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 ?-cell proliferation are present in the nuclear compartment. This observation may provide an explanation for the refractoriness of human ?-cells to proliferation. Thus, in addition to known obstacles to human ?-cell proliferation, restriction of G1/S molecules to the cytoplasm of the human ?-cell represents an unanticipated obstacle to therapeutic human ?-cell expansion.

SUBMITTER: Fiaschi-Taesch NM

PROVIDER: S-EPMC3712053 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Cytoplasmic-nuclear trafficking of G1/S cell cycle molecules and adult human β-cell replication: a revised model of human β-cell G1/S control.

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