title: Activation by ACA induces pluripotency in human blood progenitor cells.
abstract: Reprogramming of human somatic cells by transcription factors to pluripotent state holds great promise for regenerative medicine. However, low efficiencies of current reprogramming methods, immunogenicity and lack of understanding regarding the molecular mechanisms responsible for their generation, limits their utilization and raises questions regarding safety for therapeutic application. Here we report that ACA signaling via PI3K/Akt/mTor induces sustained de-differentiation of human blood progenitor cells leading to generation of ACA pluripotent stem cells. Blood-derived pluripotent stem cells differentiate in vitro into cell types of all three germ layers, exhibiting neuronal, liver, or endothelial characteristics. Our results reveal insight into the molecular events regulating cellular reprogramming and also indicate that pluripotency might be controlled in vivo through binding of a natural ligand(s) to ACA receptor enabling reprogramming through defined pathway(s) and providing a safe and efficient method for generation of pluripotent stem cells which could be a breakthrough in human therapeutics.
authors.affiliation: Principe Felipe Research Centre Valencia, Spain. becker-kojic@gmx.de.
authors.forename: Z A
authors.initials: ZA
authors.lastname: Becker-Kojić
authors.forename: J R
authors.initials: JR
authors.lastname: Ureña-Peralta
authors.forename: I
authors.initials: I
authors.lastname: Zipančić
authors.forename: F J
authors.initials: FJ
authors.lastname: Rodriguez-Jiménez
authors.forename: M P
authors.initials: MP
authors.lastname: Rubio
authors.forename: P
authors.initials: P
authors.lastname: Stojković
authors.forename: M G
authors.initials: MG
authors.lastname: Roselló
authors.forename: M
authors.initials: M
authors.lastname: Stojković
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001798:Blood Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D057026:Induced Pluripotent Stem Cells / Q000502:physiology* / Q000637:transplantation; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: C468767:ACA protein, human; D015703:Antigens, CD; D001798:Blood Proteins; D008562:Membrane Glycoproteins; D051966:Phospholipase C gamma