title: IGF2BP1 expression in human mesenchymal stem cells significantly affects their proliferation and is under the epigenetic control of TET1/2 demethylases.
abstract: Mesenchymal stem cells (MSCs) are a population of cells harboring in many tissues with the ability to differentiate toward many different lineages. Unraveling the molecular profile of MSCs is of great importance due to the fact that these cells are very often used in preclinical and clinical studies. We have previously reported the expression of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) an oncofetal mRNA-binding protein-in different stem cell types such as bone marrow (BM)-MSC and umbilical cord blood (UCB)-hematopoietic stem cells. Here, we demonstrate that MSCs of adipose tissue, BM, and UC origin have a differential pattern of IGF2BP1 and ten-eleven-translocate 1/2 (TET1/2) expression that could correlate with their proliferation potential. Upon IGF2BP1 interference, a significant reduction of cell proliferation is observed, accompanied by reduced expression of c-MYC and GLI1 and increased p21. We also present, for the first time, evidence that IGF2BP1 is epigenetically regulated by TET1 and TET2 demethylases. Specifically, we show that TET1 directly binds to the promoter of IGF2BP1 gene and affects the hydroxymethylation status of its promoter. These results indicate that IGF2BP1 and TET1/2 contribute to the stemness of MSCs, at least regarding their proliferative potential.
authors.affiliation: 1 Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital , Athens, Greece .
authors.forename: Louisa G
authors.initials: LG
authors.lastname: Mahaira
authors.forename: Olga
authors.initials: O
authors.lastname: Katsara
authors.forename: Efthimia
authors.initials: E
authors.lastname: Pappou
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Iliopoulou
authors.forename: Sotirios
authors.initials: S
authors.lastname: Fortis
authors.forename: Aristidis
authors.initials: A
authors.lastname: Antsaklis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Fotinopoulos
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Baxevanis
authors.forename: Michael
authors.initials: M
authors.lastname: Papamichail
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Perez
mesh_terms: D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D049308:Dioxygenases; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D006899:Mixed Function Oxygenases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C406144:IGF2BP1 protein, human; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human