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.
journal_name
Diabetesjournal_title
Diabetesauthors
Fiaschi-Taesch NM,Kleinberger JW,Salim FG,Troxell R,Wills R,Tanwir M,Casinelli G,Cox AE,Takane KK,Scott DK,Stewart AFdoi
10.2337/db12-0777subject
Has Abstractpub_date
2013-07-01 00:00:00pages
2450-9issue
7eissn
0012-1797issn
1939-327Xpii
db12-0777journal_volume
62pub_type
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