Reverse differentiation as a gene filtering tool in genome expression profiling of adipogenesis for fat marker gene selection and their analysis.

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  • Author(s): Ullah M;Ullah M; Stich S; Häupl T; Eucker J; Sittinger M; Ringe J
  • Source:
    PloS one [PLoS One] 2013 Jul 26; Vol. 8 (7), pp. e69754. Date of Electronic Publication: 2013 Jul 26 (Print Publication: 2013).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Gene Expression Profiling*; Adipogenesis/*genetics ; Adiposity/*genetics ; Biomarkers/*metabolism ; Cell Differentiation/*genetics ; Genome, Human/*genetics; Aged ; Binding Sites ; Cell Dedifferentiation/genetics ; Cell Separation ; Cluster Analysis ; Humans ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Middle Aged ; Models, Biological ; Signal Transduction/genetics ; Transcription Factors/metabolism
    • Abstract:
      Background: During mesenchymal stem cell (MSC) conversion into adipocytes, the adipogenic cocktail consisting of insulin, dexamethasone, indomethacin and 3-isobutyl-1-methylxanthine not only induces adipogenic-specific but also genes for non-adipogenic processes. Therefore, not all significantly expressed genes represent adipogenic-specific marker genes. So, our aim was to filter only adipogenic-specific out of all expressed genes. We hypothesize that exclusively adipogenic-specific genes change their expression during adipogenesis, and reverse during dedifferentiation. Thus, MSC were adipogenic differentiated and dedifferentiated.
      Results: Adipogenesis and reverse adipogenesis was verified by Oil Red O staining and expression of PPARG and FABP4. Based on GeneChips, 991 genes were differentially expressed during adipogenesis and grouped in 4 clusters. According to bioinformatic analysis the relevance of genes with adipogenic-linked biological annotations, expression sites, molecular functions, signaling pathways and transcription factor binding sites was high in cluster 1, including all prominent adipogenic genes like ADIPOQ, C/EBPA, LPL, PPARG and FABP4, moderate in clusters 2-3, and negligible in cluster 4. During reversed adipogenesis, only 782 expressed genes (clusters 1-3) were reverted, including 597 genes not reported for adipogenesis before. We identified APCDD1, CHI3L1, RARRES1 and SEMA3G as potential adipogenic-specific genes.
      Conclusion: The model system of adipogenesis linked to reverse adipogenesis allowed the filtration of 782 adipogenic-specific genes out of total 991 significantly expressed genes. Database analysis of adipogenic-specific biological annotations, transcription factors and signaling pathways further validated and valued our concept, because most of the filtered 782 genes showed affiliation to adipogenesis. Based on this approach, the selected and filtered genes would be potentially important for characterization of adipogenesis and monitoring of clinical translation for soft-tissue regeneration. Moreover, we report 4 new marker genes.
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    • Accession Number:
      0 (Biomarkers)
      0 (Transcription Factors)
    • Publication Date:
      Date Created: 20130808 Date Completed: 20140429 Latest Revision: 20211021
    • Publication Date:
      20240628
    • Accession Number:
      PMC3724870
    • Accession Number:
      10.1371/journal.pone.0069754
    • Accession Number:
      23922792