title: Acquisition of pluripotency through continued environmental influence on OCT4-induced plastic human fibroblasts.
abstract: The combination of OCT4 expression and short-term exposure to reprogramming media induces a state of transcriptional plasticity in human fibroblasts, capable of responding to changes in the extracellular environment that facilitate direct cell fate conversion toward lineage specific progenitors. Here we reveal that continued exposure of OCT4-induced plastic human fibroblasts to reprogramming media (RM) is sufficient to induce pluripotency. OCT4-derived induced pluripotent stem cell (iPSC(OCT4)) colonies emerged after prolonged culture in RM, and formed independently of lineage specific progenitors. Human iPSC(OCT4) are morphologically indistinguishable from conventionally derived iPSCs and express core proteins involved in maintenance of pluripotency. iPSC(OCT4) display in vivo functional pluripotency as measured by teratoma formation consisting of the three germ layers, and are capable of targeted in vitro differentiation. Our study indicates that acquisition of pluripotency is one of multiple cell fate choices that can be facilitated through environmental stimulation of OCT4-induced plasticity, and suggests the role of other reprogramming factors to induce pluripotency can be substituted by prolonged culture of plastic fibroblasts.
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. Electronic address: salcik@mcmaster.ca.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Salci
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada. Electronic address: leejung@mcmaster.ca.
authors.forename: Jung Bok
authors.initials: JB
authors.lastname: Lee
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. Electronic address: mitcherr@mcmaster.ca.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Mitchell
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada. Electronic address: lorland@mcmaster.ca.
authors.forename: Luca
authors.initials: L
authors.lastname: Orlando
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada. Electronic address: fiebiga@mcmaster.ca.
authors.forename: Aline
authors.initials: A
authors.lastname: Fiebig-Comyn
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada. Electronic address: shapovz@mcmaster.ca.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Shapovalova
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. Electronic address: mbhatia@mcmaster.ca.
authors.forename: Mickie
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000328:Adult; D000818:Animals; D019070:Cell Lineage / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008954:Models, Biological; D050814:Octamer Transcription Factor-3 / Q000494:pharmacology*
chemical_list: D050814:Octamer Transcription Factor-3