SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73

Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit extensive lineage plasticity in vitro and in vivo. Here we visualize these rare ePS cells in a latent state, i.e. lacking SOX2, OCT3/4 and NANOG (SON) expression, in non-diseased breast specimens through immunohistochem...

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Bibliographic Details
Published in:Cellular signalling 2016-12, Vol.28 (12), p.1923-1932
Main Authors: Pan, Deng, Roy, Somdutta, Gascard, Philippe, Zhao, Jianxin, Chen-Tanyolac, Chira, Tlsty, Thea D
Format: Article
Language:English
Subjects:
5'-Nucleotidase - metabolism
Adenosine - metabolism
Adult
Animals
Autocrine Communication
Biomarkers - metabolism
Breast - metabolism
Cell Differentiation
Cell Plasticity
Cyclic AMP-Dependent Protein Kinases - metabolism
Feeder Cells - cytology
Female
Fibroblast Growth Factor 2 - metabolism
GPI-Linked Proteins - metabolism
Human Embryonic Stem Cells - metabolism
Humans
Immunohistochemistry
Interleukin-6 - metabolism
Mice
Nanog Homeobox Protein - metabolism
Octamer Transcription Factor-3 - metabolism
Receptor, Adenosine A2B - metabolism
Signal Transduction
SOXB1 Transcription Factors - metabolism
STAT3 Transcription Factor - metabolism
Thy-1 Antigens - metabolism
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Summary:Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit extensive lineage plasticity in vitro and in vivo. Here we visualize these rare ePS cells in a latent state, i.e. lacking SOX2, OCT3/4 and NANOG (SON) expression, in non-diseased breast specimens through immunohistochemical analysis of previously identified ePS-specific biomarkers (CD73 , EpCAM and CD90 ). We also report a novel mechanism by which these latent ePS cells acquire SON expression and plasticity in vitro. Four extracellular factors are necessary for the acquisition of SON expression and lineage plasticity in ePS cells: adenosine (which is produced by the 5' ecto-nucleotidase CD73 and activates in turn the PKA-dependent IL6/STAT3 pathway through the adenosine receptor ADORA2b), IL6, FGF2 and ACTIVIN A. Blocking any pathway component renders ePS cells incapable of SON expression and lineage plasticity. Notably, hESCs do not use adenosine or IL6 nor they express CD73 or ADORA2b and inhibition of adenosine signaling does not ablate their plasticity. Therefore, the data presented here delineate novel circuitry and physiological signals for accessing SON expression in rare, undifferentiated human cells.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2016.09.008