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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Molecular Phenotyping of Telomerized Human Bone Marrow Skeletal Stem Cells Reveals a Genetic Program of Enhanced Proliferation and Maintenance of Differentiation Responses
JBMR Plus, Volume 2, No. 5, Year 2018
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Description
Long-term in vitro expansion of bone marrow stromal (skeletal) stem cells (also known as human mesenchymal stem cells [hMSC]) is associated with replicative senescence and impaired functions. We have previously reported that telomerization of hMSC through hTERT overexpression led to bypassing a replicative senescence phenotype and improved in vitro and in vivo functions. However, the molecular consequence of telomerization is poorly characterized. Thus, we compared the molecular phenotype of a well-studied telomerized hMSC (hMSC-TERT) cell line with primary hMSC. At a cellular level, both cell populations exhibited strong concordance for the known hMSC CD markers, similar responses to osteoblast (OB) differentiation induction, and formed heterotopic bone in vivo. Overall gene expression was highly correlated between both cell types with an average Pearson's correlation coefficient (R2) between the gene expression of all primary hMSC and all hMSC-TERT samples of 0.95 (range 0.93–0.96). Quantitative analysis of gene expression of CD markers, OB cell markers, and transcription factors (TF) showed a high degree of similarity between the two cell populations (72%, 77%, and 81%, respectively). The hMSC-TERT population was enriched mainly for genes associated with cell cycle and cell cycle signaling when compared with primary hMSC. Other enrichment was observed for genes involved in cell adhesion and skeletal system development and immune response pathways. Interestingly, hMSC-TERT shared a telomerization signature with upregulation of cancer/testis antigens, MAGE, and PAGE genes. Our data demonstrate that the enhanced biological characteristics of hMSC after telomerization are mainly due to enhanced expression of cell proliferation genes, whereas gene expression responses to differentiation are maintained. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Authors & Co-Authors
Twine, Natalie A.
Australia, Sydney
Unsw Sydney
Australia, Canberra
Commonwealth Scientific and Industrial Research Organisation
Harkness, Linda
Denmark, Odense
Odense Universitetshospital
Australia, Brisbane
The University of Queensland
Adjaye, James A.
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Aldahmash, Abdullah M.
Saudi Arabia, Riyadh
King Saud University
Wilkins, Marc R.
Australia, Sydney
Unsw Sydney
Kassem, Moustapha S.
Australia, Sydney
Unsw Sydney
Denmark, Odense
Odense Universitetshospital
Saudi Arabia, Riyadh
King Saud University
Statistics
Citations: 18
Authors: 6
Affiliations: 6
Identifiers
Doi:
10.1002/jbm4.10050
e-ISSN:
24734039
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Study Approach
Quantitative