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Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas

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...

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Autores principales: Fiaschi-Taesch, Nathalie M., Kleinberger, Jeffrey W., Salim, Fatimah G., Troxell, Ronnie, Wills, Rachel, Tanwir, Mansoor, Casinelli, Gabriella, Cox, Amy E., Takane, Karen K., Scott, Donald K., Stewart, Andrew F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712053/
https://www.ncbi.nlm.nih.gov/pubmed/23493570
http://dx.doi.org/10.2337/db12-0777
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author Fiaschi-Taesch, Nathalie M.
Kleinberger, Jeffrey W.
Salim, Fatimah G.
Troxell, Ronnie
Wills, Rachel
Tanwir, Mansoor
Casinelli, Gabriella
Cox, Amy E.
Takane, Karen K.
Scott, Donald K.
Stewart, Andrew F.
author_facet Fiaschi-Taesch, Nathalie M.
Kleinberger, Jeffrey W.
Salim, Fatimah G.
Troxell, Ronnie
Wills, Rachel
Tanwir, Mansoor
Casinelli, Gabriella
Cox, Amy E.
Takane, Karen K.
Scott, Donald K.
Stewart, Andrew F.
author_sort Fiaschi-Taesch, Nathalie M.
collection PubMed
description 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.
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spelling pubmed-37120532014-07-01 Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas Fiaschi-Taesch, Nathalie M. Kleinberger, Jeffrey W. Salim, Fatimah G. Troxell, Ronnie Wills, Rachel Tanwir, Mansoor Casinelli, Gabriella Cox, Amy E. Takane, Karen K. Scott, Donald K. Stewart, Andrew F. Diabetes Original Research 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. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712053/ /pubmed/23493570 http://dx.doi.org/10.2337/db12-0777 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Fiaschi-Taesch, Nathalie M.
Kleinberger, Jeffrey W.
Salim, Fatimah G.
Troxell, Ronnie
Wills, Rachel
Tanwir, Mansoor
Casinelli, Gabriella
Cox, Amy E.
Takane, Karen K.
Scott, Donald K.
Stewart, Andrew F.
Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas
title Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas
title_full Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas
title_fullStr Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas
title_full_unstemmed Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas
title_short Human Pancreatic β-Cell G1/S Molecule Cell Cycle Atlas
title_sort human pancreatic β-cell g1/s molecule cell cycle atlas
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712053/
https://www.ncbi.nlm.nih.gov/pubmed/23493570
http://dx.doi.org/10.2337/db12-0777
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