title: MEK and TGF-beta Inhibition Promotes Reprogramming without the Use of Transcription Factor.
abstract: The possibility of replacing the originally discovered and widely used DNA reprogramming transcription factors is stimulating enormous effort to identify more effective compounds that would not alter the genetic information. Here, we describe the generation of induced pluripotent stem cells (iPSc) from head-derived primary culture of mouse embryonic cells using small chemical inhibitors of the MEK and TGF-beta pathways without delivery of exogenous transcription factors. These iPSc express standard pluripotency markers and retain their potential to differentiate into cells of all germ layers. Our data indicate that head-derived embryonic neural cells might have the reprogramming potential while neither the same primary cells cultivated over five passages in vitro nor a cell population derived from adult brain possesses this capacity. Our results reveal the potential for small molecules to functionally replace routinely used transcription factors and lift the veil on molecular regulation controlling pluripotency. The conditions described here could provide a platform upon which other genome non integrative and safer reprogramming processes could be developed. This work also shows novel potential for developing embryonic neural cells.
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Vrbsky
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Tamas
authors.initials: T
authors.lastname: Tereh
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Kyrylenko
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Dvorak
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlarska 2, 602 00, Brno, Czech Republic.
authors.forename: Lumir
authors.initials: L
authors.lastname: Krejci
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D065150:Cellular Reprogramming; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D016212:Transforming Growth Factor beta