title: CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons.
abstract: Recent studies demonstrate that astroglia from non-neurogenic brain regions can be reprogrammed into functional neurons through forced expression of neurogenic factors. Here we explored the effect of CEND1 and NEUROG2 on reprogramming of mouse cortical astrocytes and embryonic fibroblasts. Forced expression of CEND1, NEUROG2, or both resulted in acquisition of induced neuronal cells expressing subtype-specific markers, while long-term live-cell imaging highlighted the existence of two different modes of neuronal trans-differentiation. Of note, a subpopulation of CEND1 and NEUROG2 double-transduced astrocytes formed spheres exhibiting neural stem cell properties. mRNA and protein expression studies revealed a reciprocal feedback loop existing between the two molecules, while knockdown of endogenous CEND1 demonstrated that it is a key mediator of NEUROG2-driven neuronal reprogramming. Our data suggest that common reprogramming mechanisms exist driving the conversion of lineage-distant somatic cell types to neurons and reveal a critical role for CEND1 in NEUROG2-driven astrocytic reprogramming.
authors: Department of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, Greece.
authors: Katerina
authors: K
authors: Aravantinou-Fatorou
authors: Research Group Adult Neurogenesis and Cellular Reprogramming, Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
authors: Felipe
authors: F
authors: Ortega
authors: Department of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, Greece; Department of Neurology, Laboratory of Experimental Neurophysiology, University of Athens Medical School, Eginition Hospital, 72-74 Vasilissis Sofias Avenue, Athens 11521, Greece.
authors: Dafni
authors: D
authors: Chroni-Tzartou
authors: Department of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, Greece.
authors: Nasia
authors: N
authors: Antoniou
authors: Department of Neurology, Laboratory of Experimental Neurophysiology, University of Athens Medical School, Eginition Hospital, 72-74 Vasilissis Sofias Avenue, Athens 11521, Greece.
authors: Cornelia
authors: C
authors: Poulopoulou
authors: Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efessiou Street, Athens 11527, Greece.
authors: Panagiotis K
authors: PK
authors: Politis
authors: Research Group Adult Neurogenesis and Cellular Reprogramming, Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
authors: Benedikt
authors: B
authors: Berninger
authors: Department of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, Greece.
authors: Rebecca
authors: R
authors: Matsas
authors: Department of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, Greece. Electronic address: thomaidou@pasteur.gr.
authors: Dimitra
authors: D
authors: Thomaidou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C496858:Cend1 protein, mouse; C102938:Neurog2 protein, mouse