Expression of Progenitor Cell Markers During Expansion of Sorted Human Pancreatic Beta Cells
Functional pancreatic beta cell mass is dynamic and although fully differentiated, beta cells are capable of reentering the cell cycle upon appropriate stimuli. Stimulating regeneration-competent cells in situ is clearly the most desirable way to restore damaged tissue. Regeneration by dedifferentia...
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Veröffentlicht in: | Gene expression 2005-02, Vol.12 (2), p.83-98 |
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creator | BOUCKENOOGHE, THOMAS VANDEWALLE, BRIGITTE MOERMAN, ERICKA DANZÉ, PIERRE-MARIE LUKOWIAK, BRUNO MUHARRAM, GHAFFAR KERR-CONTE, JULIE GMYR, VALERY LAINE, BERNARD PATTOU, FRANÇOIS |
description | Functional pancreatic beta cell mass is dynamic and although fully differentiated, beta cells are capable of reentering the cell cycle upon appropriate stimuli. Stimulating regeneration-competent cells in situ is clearly the most desirable way to restore damaged tissue. Regeneration
by dedifferentiation and transdifferentiation is a potential source of cells exhibiting a more developmentally immature phenotype and a wide differentiation potential. In this context and to gain a better understanding of the transformation induced in human beta cells during forced in vitro
expansion, we focused on identifying differences in gene expression along with phenotypical transformation between proliferating and quiescent human beta cells. FACS-purified beta cells from three different human pancreata were cultured during 3-4 months (8-10 subcultures) on HTB-9
cell matrix with hepatocyte growth factor. Gene expression profiling was performed on cells from each subculture on "in-house" pancreas-specific microarrays consisting of 218 genes and concomitant morphological transformations were studied by immunocytochemistry. Immunocytochemical
studies indicated a shift from epithelial to neuroepithelial cell phenotype, including progenitor cell features such as protein gene product 9.5 (PGP 9.5), Reg, vimentin, and neurogenin 3 protein expression. The expression of 49 genes was downregulated, including several markers of endocrine
differentiation while 76 were induced by cell expansion including several markers of progenitor cells. Their pattern also argues for the transdifferentiation of beta cells into progenitor cells, demonstrating neuroepithelial features and overexpressing both PBX1, a homeodomain protein that
can bind as a heterodimer with PDX1 and could switch the nature of its transcriptional activity, and neurogenin 3, a key factor for the generation of endocrine islet cells. Our study of the machinery that regulates human beta cell expansion and dedifferentiation may help elucidate some of
the critical genes that control the formation of adult pancreatic progenitor cells and hence design targets to modify their expression in view of the production of insulin-secreting cells. |
doi_str_mv | 10.3727/000000005783992151 |
format | Article |
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by dedifferentiation and transdifferentiation is a potential source of cells exhibiting a more developmentally immature phenotype and a wide differentiation potential. In this context and to gain a better understanding of the transformation induced in human beta cells during forced in vitro
expansion, we focused on identifying differences in gene expression along with phenotypical transformation between proliferating and quiescent human beta cells. FACS-purified beta cells from three different human pancreata were cultured during 3-4 months (8-10 subcultures) on HTB-9
cell matrix with hepatocyte growth factor. Gene expression profiling was performed on cells from each subculture on "in-house" pancreas-specific microarrays consisting of 218 genes and concomitant morphological transformations were studied by immunocytochemistry. Immunocytochemical
studies indicated a shift from epithelial to neuroepithelial cell phenotype, including progenitor cell features such as protein gene product 9.5 (PGP 9.5), Reg, vimentin, and neurogenin 3 protein expression. The expression of 49 genes was downregulated, including several markers of endocrine
differentiation while 76 were induced by cell expansion including several markers of progenitor cells. Their pattern also argues for the transdifferentiation of beta cells into progenitor cells, demonstrating neuroepithelial features and overexpressing both PBX1, a homeodomain protein that
can bind as a heterodimer with PDX1 and could switch the nature of its transcriptional activity, and neurogenin 3, a key factor for the generation of endocrine islet cells. Our study of the machinery that regulates human beta cell expansion and dedifferentiation may help elucidate some of
the critical genes that control the formation of adult pancreatic progenitor cells and hence design targets to modify their expression in view of the production of insulin-secreting cells.</description><identifier>ISSN: 1052-2166</identifier><identifier>EISSN: 1555-3884</identifier><identifier>DOI: 10.3727/000000005783992151</identifier><identifier>PMID: 15892450</identifier><language>eng</language><publisher>Elmsford, NY: Cognizant Communication Corporation</publisher><subject>Adult ; Antibodies ; Beta Cell Expansion ; Beta cells ; Biomarkers ; Biomarkers - metabolism ; Cell cycle ; Cell Differentiation ; Cells (biology) ; Cells, Cultured ; Differentiation ; DNA microarray ; DNA microarrays ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Flow cytometry ; Gene Expression ; Gene Expression Profiling ; Genes ; Genetic transformation ; Growth factors ; Hepatocyte growth factor ; Hepatocyte Growth Factor - pharmacology ; Homeobox ; Human purified beta cell ; Humans ; Immunoassay ; Immunocytochemistry ; Insulin ; Islet cells ; Islets of Langerhans - cytology ; Islets of Langerhans - metabolism ; Laboratories ; Neuroepithelial Cells - cytology ; Neuroepithelial Cells - metabolism ; Neurogenins ; Oligonucleotide Array Sequence Analysis ; Pancreas ; Phenotypes ; Progenitor cells ; Protein gene product 9.5 ; Proteins ; Regeneration ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal transduction ; Stem cells ; Stem Cells - metabolism ; Subculture ; Vimentin</subject><ispartof>Gene expression, 2005-02, Vol.12 (2), p.83-98</ispartof><rights>Copyright Xia & He Publishing 2005</rights><rights>Copyright © 2005 Cognizant Comm. Corp. 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c584t-67ac04b0b14b0508f981ba1fff92fe7c40a876be588b3e2e2efe6c5df27949743</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009112/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3054971725?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,21369,27903,27904,33723,33724,43784,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15892450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BOUCKENOOGHE, THOMAS</creatorcontrib><creatorcontrib>VANDEWALLE, BRIGITTE</creatorcontrib><creatorcontrib>MOERMAN, ERICKA</creatorcontrib><creatorcontrib>DANZÉ, PIERRE-MARIE</creatorcontrib><creatorcontrib>LUKOWIAK, BRUNO</creatorcontrib><creatorcontrib>MUHARRAM, GHAFFAR</creatorcontrib><creatorcontrib>KERR-CONTE, JULIE</creatorcontrib><creatorcontrib>GMYR, VALERY</creatorcontrib><creatorcontrib>LAINE, BERNARD</creatorcontrib><creatorcontrib>PATTOU, FRANÇOIS</creatorcontrib><title>Expression of Progenitor Cell Markers During Expansion of Sorted Human Pancreatic Beta Cells</title><title>Gene expression</title><addtitle>ge</addtitle><addtitle>Gene Expr</addtitle><description>Functional pancreatic beta cell mass is dynamic and although fully differentiated, beta cells are capable of reentering the cell cycle upon appropriate stimuli. Stimulating regeneration-competent cells in situ is clearly the most desirable way to restore damaged tissue. Regeneration
by dedifferentiation and transdifferentiation is a potential source of cells exhibiting a more developmentally immature phenotype and a wide differentiation potential. In this context and to gain a better understanding of the transformation induced in human beta cells during forced in vitro
expansion, we focused on identifying differences in gene expression along with phenotypical transformation between proliferating and quiescent human beta cells. FACS-purified beta cells from three different human pancreata were cultured during 3-4 months (8-10 subcultures) on HTB-9
cell matrix with hepatocyte growth factor. Gene expression profiling was performed on cells from each subculture on "in-house" pancreas-specific microarrays consisting of 218 genes and concomitant morphological transformations were studied by immunocytochemistry. Immunocytochemical
studies indicated a shift from epithelial to neuroepithelial cell phenotype, including progenitor cell features such as protein gene product 9.5 (PGP 9.5), Reg, vimentin, and neurogenin 3 protein expression. The expression of 49 genes was downregulated, including several markers of endocrine
differentiation while 76 were induced by cell expansion including several markers of progenitor cells. Their pattern also argues for the transdifferentiation of beta cells into progenitor cells, demonstrating neuroepithelial features and overexpressing both PBX1, a homeodomain protein that
can bind as a heterodimer with PDX1 and could switch the nature of its transcriptional activity, and neurogenin 3, a key factor for the generation of endocrine islet cells. Our study of the machinery that regulates human beta cell expansion and dedifferentiation may help elucidate some of
the critical genes that control the formation of adult pancreatic progenitor cells and hence design targets to modify their expression in view of the production of insulin-secreting cells.</description><subject>Adult</subject><subject>Antibodies</subject><subject>Beta Cell Expansion</subject><subject>Beta cells</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Cell cycle</subject><subject>Cell Differentiation</subject><subject>Cells (biology)</subject><subject>Cells, Cultured</subject><subject>Differentiation</subject><subject>DNA microarray</subject><subject>DNA microarrays</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>Flow cytometry</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Genetic transformation</subject><subject>Growth factors</subject><subject>Hepatocyte growth factor</subject><subject>Hepatocyte Growth Factor - pharmacology</subject><subject>Homeobox</subject><subject>Human purified beta cell</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Immunocytochemistry</subject><subject>Insulin</subject><subject>Islet cells</subject><subject>Islets of Langerhans - cytology</subject><subject>Islets of Langerhans - metabolism</subject><subject>Laboratories</subject><subject>Neuroepithelial Cells - cytology</subject><subject>Neuroepithelial Cells - metabolism</subject><subject>Neurogenins</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pancreas</subject><subject>Phenotypes</subject><subject>Progenitor cells</subject><subject>Protein gene product 9.5</subject><subject>Proteins</subject><subject>Regeneration</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Stem Cells - 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metabolism</topic><topic>Cell cycle</topic><topic>Cell Differentiation</topic><topic>Cells (biology)</topic><topic>Cells, Cultured</topic><topic>Differentiation</topic><topic>DNA microarray</topic><topic>DNA microarrays</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Flow cytometry</topic><topic>Gene Expression</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Genetic transformation</topic><topic>Growth factors</topic><topic>Hepatocyte growth factor</topic><topic>Hepatocyte Growth Factor - pharmacology</topic><topic>Homeobox</topic><topic>Human purified beta cell</topic><topic>Humans</topic><topic>Immunoassay</topic><topic>Immunocytochemistry</topic><topic>Insulin</topic><topic>Islet cells</topic><topic>Islets of Langerhans - cytology</topic><topic>Islets of Langerhans - metabolism</topic><topic>Laboratories</topic><topic>Neuroepithelial Cells - cytology</topic><topic>Neuroepithelial Cells - metabolism</topic><topic>Neurogenins</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pancreas</topic><topic>Phenotypes</topic><topic>Progenitor cells</topic><topic>Protein gene product 9.5</topic><topic>Proteins</topic><topic>Regeneration</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal transduction</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Subculture</topic><topic>Vimentin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BOUCKENOOGHE, THOMAS</creatorcontrib><creatorcontrib>VANDEWALLE, BRIGITTE</creatorcontrib><creatorcontrib>MOERMAN, ERICKA</creatorcontrib><creatorcontrib>DANZÉ, PIERRE-MARIE</creatorcontrib><creatorcontrib>LUKOWIAK, BRUNO</creatorcontrib><creatorcontrib>MUHARRAM, GHAFFAR</creatorcontrib><creatorcontrib>KERR-CONTE, JULIE</creatorcontrib><creatorcontrib>GMYR, VALERY</creatorcontrib><creatorcontrib>LAINE, BERNARD</creatorcontrib><creatorcontrib>PATTOU, FRANÇOIS</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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Stimulating regeneration-competent cells in situ is clearly the most desirable way to restore damaged tissue. Regeneration
by dedifferentiation and transdifferentiation is a potential source of cells exhibiting a more developmentally immature phenotype and a wide differentiation potential. In this context and to gain a better understanding of the transformation induced in human beta cells during forced in vitro
expansion, we focused on identifying differences in gene expression along with phenotypical transformation between proliferating and quiescent human beta cells. FACS-purified beta cells from three different human pancreata were cultured during 3-4 months (8-10 subcultures) on HTB-9
cell matrix with hepatocyte growth factor. Gene expression profiling was performed on cells from each subculture on "in-house" pancreas-specific microarrays consisting of 218 genes and concomitant morphological transformations were studied by immunocytochemistry. Immunocytochemical
studies indicated a shift from epithelial to neuroepithelial cell phenotype, including progenitor cell features such as protein gene product 9.5 (PGP 9.5), Reg, vimentin, and neurogenin 3 protein expression. The expression of 49 genes was downregulated, including several markers of endocrine
differentiation while 76 were induced by cell expansion including several markers of progenitor cells. Their pattern also argues for the transdifferentiation of beta cells into progenitor cells, demonstrating neuroepithelial features and overexpressing both PBX1, a homeodomain protein that
can bind as a heterodimer with PDX1 and could switch the nature of its transcriptional activity, and neurogenin 3, a key factor for the generation of endocrine islet cells. Our study of the machinery that regulates human beta cell expansion and dedifferentiation may help elucidate some of
the critical genes that control the formation of adult pancreatic progenitor cells and hence design targets to modify their expression in view of the production of insulin-secreting cells.</abstract><cop>Elmsford, NY</cop><pub>Cognizant Communication Corporation</pub><pmid>15892450</pmid><doi>10.3727/000000005783992151</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Antibodies Beta Cell Expansion Beta cells Biomarkers Biomarkers - metabolism Cell cycle Cell Differentiation Cells (biology) Cells, Cultured Differentiation DNA microarray DNA microarrays Epithelial Cells - cytology Epithelial Cells - metabolism Flow cytometry Gene Expression Gene Expression Profiling Genes Genetic transformation Growth factors Hepatocyte growth factor Hepatocyte Growth Factor - pharmacology Homeobox Human purified beta cell Humans Immunoassay Immunocytochemistry Insulin Islet cells Islets of Langerhans - cytology Islets of Langerhans - metabolism Laboratories Neuroepithelial Cells - cytology Neuroepithelial Cells - metabolism Neurogenins Oligonucleotide Array Sequence Analysis Pancreas Phenotypes Progenitor cells Protein gene product 9.5 Proteins Regeneration Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism Signal transduction Stem cells Stem Cells - metabolism Subculture Vimentin |
title | Expression of Progenitor Cell Markers During Expansion of Sorted Human Pancreatic Beta Cells |
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