title: An ES-like pluripotent state in FGF-dependent murine iPS cells.
abstract: Recent data demonstrates that stem cells can exist in two morphologically, molecularly and functionally distinct pluripotent states; a naïve LIF-dependent pluripotent state which is represented by murine embryonic stem cells (mESCs) and an FGF-dependent primed pluripotent state represented by murine and rat epiblast stem cells (EpiSCs). We find that derivation of induced pluripotent stem cells (iPSCs) under EpiSC culture conditions yields FGF-dependent iPSCs from hereon called FGF-iPSCs) which, unexpectedly, display naïve ES-like/ICM properties. FGF-iPSCs display X-chromosome activation, multi-lineage differentiation, teratoma competence and chimera contribution in vivo. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions. Characterization of the key molecular signalling pathways revealed FGF-iPSCs to depend on the Activin/Nodal and FGF pathways, while signalling through the JAK-STAT pathway is not required for FGF-iPS cell maintenance. Our findings suggest that in 129 and Bl6 mouse strains, iPSCs can dominantly adopt a naive pluripotent state regardless of culture growth factor conditions.
authors.affiliation: Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Di Stefano
authors.forename: Christa
authors.initials: C
authors.lastname: Buecker
authors.forename: Federica
authors.initials: F
authors.lastname: Ungaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prigione
authors.forename: Hsu-Hsin
authors.initials: HH
authors.lastname: Chen
authors.forename: Maaike
authors.initials: M
authors.lastname: Welling
authors.forename: Maureen
authors.initials: M
authors.lastname: Eijpe
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mostoslavsky
authors.forename: Paul
authors.initials: P
authors.lastname: Tesar
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
authors.forename: Niels
authors.initials: N
authors.lastname: Geijsen
authors.forename: Vania
authors.initials: V
authors.lastname: Broccoli
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D046149:Embryo Culture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012190:Retroviridae / Q000235:genetics; D013045:Species Specificity; D013724:Teratoma / Q000235:genetics; D014960:X Chromosome
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors