Gene profiling of bone marrow- and adipose tissue-derived stromal cells: a key role of Kruppel-like factor 4 in cell fate regulation

Abstract Background aims Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study...

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Veröffentlicht in:Cytotherapy (Oxford, England) England), 2011-03, Vol.13 (3), p.329-340
Hauptverfasser: Saulnier, Nathalie, Puglisi, Maria A, Lattanzi, Wanda, Castellini, Laura, Pani, Giovambattista, Leone, Giuseppe, Alfieri, Sergio, Michetti, Fabrizio, Piscaglia, Anna Chiara, Gasbarrini, Antonio
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container_issue 3
container_start_page 329
container_title Cytotherapy (Oxford, England)
container_volume 13
creator Saulnier, Nathalie
Puglisi, Maria A
Lattanzi, Wanda
Castellini, Laura
Pani, Giovambattista
Leone, Giuseppe
Alfieri, Sergio
Michetti, Fabrizio
Piscaglia, Anna Chiara
Gasbarrini, Antonio
description Abstract Background aims Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core. Methods Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR. Results We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity. Conclusions Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state.
doi_str_mv 10.3109/14653249.2010.515576
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However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core. Methods Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR. Results We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity. Conclusions Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state.</description><identifier>ISSN: 1465-3249</identifier><identifier>EISSN: 1477-2566</identifier><identifier>DOI: 10.3109/14653249.2010.515576</identifier><identifier>PMID: 20849362</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Adipose Tissue - cytology ; adipose tissue stromal cells ; Adult ; Advanced Basic Science ; Binding Sites ; Bone Marrow Cells - cytology ; Bone Marrow Cells - metabolism ; bone marrow stromal cells ; Cell Differentiation - genetics ; Cell Lineage - genetics ; Chromatin Immunoprecipitation ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Knockdown Techniques ; Humans ; Kruppel-like factor 4 ; Kruppel-Like Transcription Factors - genetics ; Kruppel-Like Transcription Factors - metabolism ; Male ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; microarray ; Middle Aged ; Models, Biological ; Other ; Polymerase Chain Reaction ; Promoter Regions, Genetic - genetics ; Protein Binding ; Reproducibility of Results ; Stromal Cells - cytology ; Stromal Cells - metabolism ; Young Adult</subject><ispartof>Cytotherapy (Oxford, England), 2011-03, Vol.13 (3), p.329-340</ispartof><rights>International Society for Cellular Therapy</rights><rights>2011 International Society for Cellular Therapy</rights><rights>2011 Informa Healthcare 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-28abddd204fc2e72316b6183026b28719b397353e4d03a86a90fa9ed89f5c3a03</citedby><cites>FETCH-LOGICAL-c471t-28abddd204fc2e72316b6183026b28719b397353e4d03a86a90fa9ed89f5c3a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20849362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saulnier, Nathalie</creatorcontrib><creatorcontrib>Puglisi, Maria A</creatorcontrib><creatorcontrib>Lattanzi, Wanda</creatorcontrib><creatorcontrib>Castellini, Laura</creatorcontrib><creatorcontrib>Pani, Giovambattista</creatorcontrib><creatorcontrib>Leone, Giuseppe</creatorcontrib><creatorcontrib>Alfieri, Sergio</creatorcontrib><creatorcontrib>Michetti, Fabrizio</creatorcontrib><creatorcontrib>Piscaglia, Anna Chiara</creatorcontrib><creatorcontrib>Gasbarrini, Antonio</creatorcontrib><title>Gene profiling of bone marrow- and adipose tissue-derived stromal cells: a key role of Kruppel-like factor 4 in cell fate regulation</title><title>Cytotherapy (Oxford, England)</title><addtitle>Cytotherapy</addtitle><description>Abstract Background aims Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core. Methods Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR. Results We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity. 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However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core. Methods Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR. Results We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity. Conclusions Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>20849362</pmid><doi>10.3109/14653249.2010.515576</doi><tpages>12</tpages></addata></record>
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subjects Adipose Tissue - cytology
adipose tissue stromal cells
Adult
Advanced Basic Science
Binding Sites
Bone Marrow Cells - cytology
Bone Marrow Cells - metabolism
bone marrow stromal cells
Cell Differentiation - genetics
Cell Lineage - genetics
Chromatin Immunoprecipitation
Female
Gene Expression Profiling
Gene Expression Regulation
Gene Knockdown Techniques
Humans
Kruppel-like factor 4
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Male
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
microarray
Middle Aged
Models, Biological
Other
Polymerase Chain Reaction
Promoter Regions, Genetic - genetics
Protein Binding
Reproducibility of Results
Stromal Cells - cytology
Stromal Cells - metabolism
Young Adult
title Gene profiling of bone marrow- and adipose tissue-derived stromal cells: a key role of Kruppel-like factor 4 in cell fate regulation
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