title: Effects of erythropoietin in murine-induced pluripotent cell-derived panneural progenitor cells.
abstract: Induced cell fate changes by reprogramming of somatic cells offers an efficient strategy to generate autologous pluripotent stem (iPS) cells from any adult cell type. The potential of iPS cells to differentiate into various cell types is well established, however the efficiency to produce functional neurons from iPS cells remains modest. Here, we generated panneural progenitor cells (pNPCs) from mouse iPS cells and investigated the effect of the neurotrophic growth factor erythropoietin (EPO) on their survival, proliferation and neurodifferentiation. Under neural differentiation conditions, iPS-derived pNPCs gave rise to microtubule-associated protein-2 positive neuronlike cells (34% to 43%) and platelet-derived growth factor receptor positive oligodendrocytelike cells (21% to 25%) while less than 1% of the cells expressed the astrocytic marker glial fibrillary acidic protein. Neuronlike cells generated action potentials and developed active presynaptic terminals. The pNPCs expressed EPO receptor (EPOR) mRNA and displayed functional EPOR signaling. In proliferating cultures, EPO (0.1-3 U/mL) slightly improved pNPC survival but reduced cell proliferation and neurosphere formation in a concentration-dependent manner. In differentiating cultures EPO facilitated neurodifferentiation as assessed by the increased number of β-III-tubulin positive neurons. Our results show that EPO inhibits iPS pNPC self-renewal and promotes neurogenesis.
authors.affiliation: Department of Neurosurgery, University of Würzburg, Würzburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Offen
authors.affiliation: Department of Neurosurgery, University of Würzburg, Würzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Flemming
authors.affiliation: Department of Neurosurgery, University of Würzburg, Würzburg, Germany.
authors.forename: Hares
authors.initials: H
authors.lastname: Kamawal
authors.affiliation: Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, Würzburg, Germany.
authors.forename: Ruhel
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Department of Neurosurgery, University of Würzburg, Würzburg, Germany.
authors.forename: Wanja
authors.initials: W
authors.lastname: Wolber
authors.affiliation: Department of Neurology, University of Würzburg, Würzburg, Germany Department of Neurology and Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Geis
authors.affiliation: Department of Cell and Developmental Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
authors.affiliation: Department of Cell and Developmental Biology, Max-Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.affiliation: Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, Würzburg, Germany.
authors.forename: Albrecht M
authors.initials: AM
authors.lastname: Müller
authors.affiliation: Department of Neurosurgery, University of Würzburg, Würzburg, Germany.
authors.forename: Anna-Leena
authors.initials: AL
authors.lastname: Sirén
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D004921:Erythropoietin / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055366:Synaptic Potentials
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D004921:Erythropoietin; D017479:Receptors, Platelet-Derived Growth Factor