Gene expression analysis of hematopoietic progenitor cells identifies Dlg7 as a potential stem cell gene

2.50
Hdl Handle:
http://hdl.handle.net/2336/14503
Title:
Gene expression analysis of hematopoietic progenitor cells identifies Dlg7 as a potential stem cell gene
Authors:
Gudmundsson, Kristbjorn Orri; Thorsteinsson, Leifur; Sigurjonsson, Olafur E; Keller, Jonathan R; Olafsson, Karl; Egeland, Torstein; Gudmundsson, Sveinn; Rafnar, Thorunn
Citation:
Stem Cells 2007, 25(6):1498-506
Issue Date:
1-Jun-2007
Abstract:
Inducible hematopoietic stem/progenitor cell lines represent a model for studying genes involved in self-renewal and differentiation. Here, gene expression was studied in the inducible human CD34+ acute myelogenous leukemia cell line KG1 using oligonucleotide arrays and suppression subtractive cloning. Using this approach, we identified Dlg7, the homolog of the Drosophila Dlg1 tumor suppressor gene, as downregulated at the early stages of KG1 differentiation. Similarly, Dlg7 was expressed in normal purified umbilical cord blood CD34+CD38- progenitors but not in the more committed CD34+CD38+ population. Dlg7 expression was not detected in differentiated cells obtained from hematopoietic colonies, nor was expression detected in purified T-cells, B-cells, and monocytes. When analyzed in different types of stem cells, Dlg7 expression was detected in purified human bone marrow-derived CD133+ progenitor cells, human mesenchymal stem cells, and mouse embryonic stem (ES) cells. Overexpression of Dlg7 in mouse ES cells increased their growth rate and reduced the number of EBs emerging upon differentiation. In addition, the EBs were significantly smaller, indicating an inhibition in differentiation. This inhibition was further supported by higher expression of Bmp4, Oct4, Rex1, and Nanog in EBs overexpressing Dlg7 and lower expression of Brachyury. Finally, the Dlg7 protein was detected in liver and colon carcinoma tumors but not in normal adjacent tissues, suggesting a role for the gene in carcinogenesis. In conclusion, our results suggest that Dlg7 has a role in stem cell survival, in maintaining stem cell properties, and in carcinogenesis. Disclosure of potential conflicts of interest is found at the end of this article.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://stemcells.alphamedpress.org/cgi/content/abstract/25/6/1498

Full metadata record

DC FieldValue Language
dc.contributor.authorGudmundsson, Kristbjorn Orri-
dc.contributor.authorThorsteinsson, Leifur-
dc.contributor.authorSigurjonsson, Olafur E-
dc.contributor.authorKeller, Jonathan R-
dc.contributor.authorOlafsson, Karl-
dc.contributor.authorEgeland, Torstein-
dc.contributor.authorGudmundsson, Sveinn-
dc.contributor.authorRafnar, Thorunn-
dc.date.accessioned2007-11-08T08:39:57Z-
dc.date.available2007-11-08T08:39:57Z-
dc.date.issued2007-06-01-
dc.date.submitted2007-11-08-
dc.identifier.citationStem Cells 2007, 25(6):1498-506en
dc.identifier.issn1066-5099-
dc.identifier.pmid17322106-
dc.identifier.doi10.1634/stemcells.2005-0479-
dc.identifier.urihttp://hdl.handle.net/2336/14503-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractInducible hematopoietic stem/progenitor cell lines represent a model for studying genes involved in self-renewal and differentiation. Here, gene expression was studied in the inducible human CD34+ acute myelogenous leukemia cell line KG1 using oligonucleotide arrays and suppression subtractive cloning. Using this approach, we identified Dlg7, the homolog of the Drosophila Dlg1 tumor suppressor gene, as downregulated at the early stages of KG1 differentiation. Similarly, Dlg7 was expressed in normal purified umbilical cord blood CD34+CD38- progenitors but not in the more committed CD34+CD38+ population. Dlg7 expression was not detected in differentiated cells obtained from hematopoietic colonies, nor was expression detected in purified T-cells, B-cells, and monocytes. When analyzed in different types of stem cells, Dlg7 expression was detected in purified human bone marrow-derived CD133+ progenitor cells, human mesenchymal stem cells, and mouse embryonic stem (ES) cells. Overexpression of Dlg7 in mouse ES cells increased their growth rate and reduced the number of EBs emerging upon differentiation. In addition, the EBs were significantly smaller, indicating an inhibition in differentiation. This inhibition was further supported by higher expression of Bmp4, Oct4, Rex1, and Nanog in EBs overexpressing Dlg7 and lower expression of Brachyury. Finally, the Dlg7 protein was detected in liver and colon carcinoma tumors but not in normal adjacent tissues, suggesting a role for the gene in carcinogenesis. In conclusion, our results suggest that Dlg7 has a role in stem cell survival, in maintaining stem cell properties, and in carcinogenesis. Disclosure of potential conflicts of interest is found at the end of this article.en
dc.language.isoenen
dc.publisherAlphaMed Pressen
dc.relation.urlhttp://stemcells.alphamedpress.org/cgi/content/abstract/25/6/1498en
dc.subject.meshAntigens, CD34en
dc.subject.meshAntigens, CD38en
dc.subject.meshBlood Cellsen
dc.subject.meshCell Differentiationen
dc.subject.meshCell Survivalen
dc.subject.meshDendritic Cellsen
dc.subject.meshGene Expression Profilingen
dc.subject.meshHematopoietic Stem Cellsen
dc.subject.meshNeoplasm Proteinsen
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshUmbilical Corden
dc.titleGene expression analysis of hematopoietic progenitor cells identifies Dlg7 as a potential stem cell geneen
dc.typeArticleen
dc.format.digYES-

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