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The Genetic Program of Pancreatic β-Cell Replication In Vivo

The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of...

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Autores principales: Klochendler, Agnes, Caspi, Inbal, Corem, Noa, Moran, Maya, Friedlich, Oriel, Elgavish, Sharona, Nevo, Yuval, Helman, Aharon, Glaser, Benjamin, Eden, Amir, Itzkovitz, Shalev, Dor, Yuval
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915587/
https://www.ncbi.nlm.nih.gov/pubmed/26993067
http://dx.doi.org/10.2337/db16-0003
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author Klochendler, Agnes
Caspi, Inbal
Corem, Noa
Moran, Maya
Friedlich, Oriel
Elgavish, Sharona
Nevo, Yuval
Helman, Aharon
Glaser, Benjamin
Eden, Amir
Itzkovitz, Shalev
Dor, Yuval
author_facet Klochendler, Agnes
Caspi, Inbal
Corem, Noa
Moran, Maya
Friedlich, Oriel
Elgavish, Sharona
Nevo, Yuval
Helman, Aharon
Glaser, Benjamin
Eden, Amir
Itzkovitz, Shalev
Dor, Yuval
author_sort Klochendler, Agnes
collection PubMed
description The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are “left behind” and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo.
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spelling pubmed-49155872017-07-01 The Genetic Program of Pancreatic β-Cell Replication In Vivo Klochendler, Agnes Caspi, Inbal Corem, Noa Moran, Maya Friedlich, Oriel Elgavish, Sharona Nevo, Yuval Helman, Aharon Glaser, Benjamin Eden, Amir Itzkovitz, Shalev Dor, Yuval Diabetes Genetics/Genomes/Proteomics/Metabolomics The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are “left behind” and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo. American Diabetes Association 2016-07 2016-03-18 /pmc/articles/PMC4915587/ /pubmed/26993067 http://dx.doi.org/10.2337/db16-0003 Text en © 2016 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.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Klochendler, Agnes
Caspi, Inbal
Corem, Noa
Moran, Maya
Friedlich, Oriel
Elgavish, Sharona
Nevo, Yuval
Helman, Aharon
Glaser, Benjamin
Eden, Amir
Itzkovitz, Shalev
Dor, Yuval
The Genetic Program of Pancreatic β-Cell Replication In Vivo
title The Genetic Program of Pancreatic β-Cell Replication In Vivo
title_full The Genetic Program of Pancreatic β-Cell Replication In Vivo
title_fullStr The Genetic Program of Pancreatic β-Cell Replication In Vivo
title_full_unstemmed The Genetic Program of Pancreatic β-Cell Replication In Vivo
title_short The Genetic Program of Pancreatic β-Cell Replication In Vivo
title_sort genetic program of pancreatic β-cell replication in vivo
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915587/
https://www.ncbi.nlm.nih.gov/pubmed/26993067
http://dx.doi.org/10.2337/db16-0003
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