NANOG priming before full reprogramming may generate germ cell tumours

Article Article scientifique Article NANOG priming before full reprogramming may generate germ cell tumours eng 2011 author Grad Iwona 585158 author Hibaoui Youssef 623159 author Jaconi Marisa author Chicha Laurie author Bergström-Tengzelius R author Sailani M R author Pelte M F author Dahoun Sophie 22913 author Mitsiadis T A author Töhönen V author Bouillaguet Serge 23861 author Antonarakis S E author Kere J author Zucchelli M author Hovatta Outi Leena Lemmikki 677103 author Feki Anis 134105 258-274; discussion 274 10.22203/ecm.v022a20 22071697 1473-2262 Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation. Animals Base Sequence Cell Differentiation Cell Line Homeodomain Proteins/metabolism Humans Induced Pluripotent Stem Cells/cytology/metabolism Karyotype Mice Mice, SCID Neoplasms, Germ Cell and Embryonal/etiology/pathology Nuclear Reprogramming Octamer Transcription Factor-3/biosynthesis/metabolism RNA-Binding Proteins/biosynthesis SOXB1 Transcription Factors/biosynthesis Sequence Analysis, RNA Dewey 576.5 Dewey 616.07 Dewey 617.6 Dewey 618 135 Département de médecine génétique et développement 21D 137 Département de pathologie et immunologie 21F 58 Département de pédiatrie, gynécologie et obstétrique 223 205 Division de cariologie et d'endodontie 24P1 false 390 Carcinome mammaire type « basal-like » 656 508 Groupe Bouillaguet Serge (medecine dentaire) 846 European cells & materials 22 1f8bbc38-cb84-4e51-b590-a5f5e9572652 Article (Published version) Restricted Pelte MF Eur Cell Mater 2011, 22, 258.pdf 750989 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine dentaire / Département de médecine dentaire préventive et de premier recours / Division de cariologie et d'endodontie

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NANOG priming before full reprogramming may generate germ cell tumours	European cells & materials			2011	739	1

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Hovatta, Outi Leena Lemmikki