Pluripotency regulators in human mesenchymal stem cells: expression of NANOG but not of OCT-4 and SOX-2.
Mesenchymal stem cells (MSCs) are adult multipotent cells able to differentiate toward mature mesodermal lineages. In spite of more than a decade of investigation, little is known about the molecular mechanisms regulating the undifferentiated state and the identity of distinct functional subpopulations in these cells. Transcription factors that regulate the maintenance of the pluripotent state in embryonic stem cells, including NANOG, SOX2, and OCT4, have been proposed to play a similar role also in adult stem cells, although with conflicting results. We performed a critical evaluation of expression of these 3 transcription factors and found that NANOG, but not OCT-4 and SOX-2, is expressed in cultured human adult MSCs. Actually, NANOG was not expressed in freshly isolated MSCs, but was detected only after in vitro culture. NANOG was detected only in proliferating cells, but not in MSCs induced to differentiate. The percentage of cells expressing NANOG was maintained throughout early passages of MSCs, but then started to decrease in late passages in MSCs from adipose tissue and heart but not from bone marrow. However, the number of NANOG-expressing cells did not associate with the proliferative and differentiative capabilities of MSC populations, neither its expression appeared to identify cells having stem or progenitor cell properties. Accordingly, we propose that activation of NANOG expression in MSCs is associated with, although cannot directly regulate, the transition from in vivo quiescence to adaptation to in vitro growth conditions.
Pierantozzi
Enrico
E
Molecular Medicine Section, Department of Neuroscience, University of Siena, Siena, Italy.
Gava
Barbara
B
Manini
Ivana
I
Roviello
Franco
F
Marotta
Giuseppe
G
Chiavarelli
Mario
M
Sorrentino
Vincenzo
V
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003470:Culture Media; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D003470:Culture Media; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors