title: Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming.
abstract: Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state. During differentiation of embryoid bodies, PML influences cell-fate decisions between mesoderm and endoderm by controlling the expression of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced pluripotent stem cells by inhibiting the transforming growth factor β pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC naive pluripotency and somatic cell reprogramming.
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece.
authors.forename: Christiana
authors.initials: C
authors.lastname: Hadjimichael
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece; Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, Alexandroupolis, Evros 68100, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Chanoumidou
authors.affiliation: Department of Biology, University of Crete, Heraklion, Crete 71409, Greece.
authors.forename: Christoforos
authors.initials: C
authors.lastname: Nikolaou
authors.affiliation: Department of Biology, University of Crete, Heraklion, Crete 71409, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Klonizakis
authors.affiliation: Department of Biology, University of Crete, Heraklion, Crete 71409, Greece.
authors.forename: Gesthimani-Ioanna
authors.initials: GI
authors.lastname: Theodosi
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece.
authors.forename: Takis
authors.initials: T
authors.lastname: Makatounakis
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece.
authors.forename: Joseph
authors.initials: J
authors.lastname: Papamatheakis
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece. Electronic address: kretsova@imbb.forth.gr.
authors.forename: Androniki
authors.initials: A
authors.lastname: Kretsovali
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004475:Ectoderm / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse; D016212:Transforming Growth Factor beta
keywords: differentiation; embryonic stem cells; induced pluripotent stem cells; pluripotency; promyelocytic leukemia protein