CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons

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 ex...

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Main Authors: Katerina Aravantinou-Fatorou, Felipe Ortega, Dafni Chroni-Tzartou, Nasia Antoniou, Cornelia Poulopoulou, Panagiotis K. Politis, Benedikt Berninger, Rebecca Matsas, Dimitra Thomaidou
Format: Article
Language:English
Published: Elsevier 2015-09-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671115002180
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author Katerina Aravantinou-Fatorou
Felipe Ortega
Dafni Chroni-Tzartou
Nasia Antoniou
Cornelia Poulopoulou
Panagiotis K. Politis
Benedikt Berninger
Rebecca Matsas
Dimitra Thomaidou
author_facet Katerina Aravantinou-Fatorou
Felipe Ortega
Dafni Chroni-Tzartou
Nasia Antoniou
Cornelia Poulopoulou
Panagiotis K. Politis
Benedikt Berninger
Rebecca Matsas
Dimitra Thomaidou
author_sort Katerina Aravantinou-Fatorou
collection DOAJ
description 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.
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spelling doaj.art-adc94e0bc89e4496a5f98c1d5f1282ef2022-12-21T19:19:52ZengElsevierStem Cell Reports2213-67112015-09-015340541810.1016/j.stemcr.2015.07.012CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated NeuronsKaterina Aravantinou-Fatorou0Felipe Ortega1Dafni Chroni-Tzartou2Nasia Antoniou3Cornelia Poulopoulou4Panagiotis K. Politis5Benedikt Berninger6Rebecca Matsas7Dimitra Thomaidou8Department of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, GreeceResearch Group Adult Neurogenesis and Cellular Reprogramming, Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, GermanyDepartment of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, GreeceDepartment of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, GreeceDepartment of Neurology, Laboratory of Experimental Neurophysiology, University of Athens Medical School, Eginition Hospital, 72–74 Vasilissis Sofias Avenue, Athens 11521, GreeceCenter for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efessiou Street, Athens 11527, GreeceResearch Group Adult Neurogenesis and Cellular Reprogramming, Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, GermanyDepartment of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, GreeceDepartment of Neurobiology, Hellenic Pasteur Institute, 127 Vasilissis Sofias Avenue, Athens 11521, GreeceRecent 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.http://www.sciencedirect.com/science/article/pii/S2213671115002180
spellingShingle Katerina Aravantinou-Fatorou
Felipe Ortega
Dafni Chroni-Tzartou
Nasia Antoniou
Cornelia Poulopoulou
Panagiotis K. Politis
Benedikt Berninger
Rebecca Matsas
Dimitra Thomaidou
CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons
Stem Cell Reports
title CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons
title_full CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons
title_fullStr CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons
title_full_unstemmed CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons
title_short CEND1 and NEUROGENIN2 Reprogram Mouse Astrocytes and Embryonic Fibroblasts to Induced Neural Precursors and Differentiated Neurons
title_sort cend1 and neurogenin2 reprogram mouse astrocytes and embryonic fibroblasts to induced neural precursors and differentiated neurons
url http://www.sciencedirect.com/science/article/pii/S2213671115002180
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