title: SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73.
abstract: 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.
authors.affiliation: University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, United States; Department of Pathology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0511, United States.
authors.forename: Deng
authors.initials: D
authors.lastname: Pan
authors.affiliation: University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, United States; Department of Pathology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0511, United States.
authors.forename: Somdutta
authors.initials: S
authors.lastname: Roy
authors.affiliation: University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, United States; Department of Pathology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0511, United States.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gascard
authors.affiliation: University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, United States; Department of Pathology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0511, United States.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, United States; Department of Pathology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0511, United States.
authors.forename: Chira
authors.initials: C
authors.lastname: Chen-Tanyolac
authors.affiliation: University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, United States; Department of Pathology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0511, United States. Electronic address: thea.tlsty@ucsf.edu.
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D000328:Adult; D000818:Animals; D019898:Autocrine Communication; D015415:Biomarkers / Q000378:metabolism; D001940:Breast / Q000378:metabolism; D002454:Cell Differentiation; D000066670:Cell Plasticity; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D061252:Feeder Cells / Q000166:cytology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D018800:Thy-1 Antigens / Q000378:metabolism
chemical_list: D015415:Biomarkers; D058851:GPI-Linked Proteins; D015850:Interleukin-6; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D043704:Receptor, Adenosine A2B; D055748:SOXB1 Transcription Factors; D050796:STAT3 Transcription Factor; D018800:Thy-1 Antigens; D016222:Fibroblast Growth Factor 2; D017868:Cyclic AMP-Dependent Protein Kinases; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D000241:Adenosine