title: Ascl1 Converts Dorsal Midbrain Astrocytes into Functional Neurons In Vivo.
abstract: In vivo induction of non-neuronal cells into neurons by transcription factors offers potential therapeutic approaches for neural regeneration. Although generation of induced neuronal (iN) cells in vitro and in vivo has been reported, whether iN cells can be fully integrated into existing circuits remains unclear. Here we show that expression of achaete-scute complex homolog-like 1 (Ascl1) alone is sufficient to convert dorsal midbrain astrocytes of mice into functional iN cells in vitro and in vivo. Specific expression of Ascl1 in astrocytes by infection with GFAP-adeno-associated virus (AAV) vector converts astrocytes in dorsal midbrain, striatum, and somatosensory cortex of postnatal and adult mice into functional neurons in vivo. These iN cells mature progressively, exhibiting neuronal morphology and markers, action potentials, and synaptic inputs from and output to existing neurons. Thus, a single transcription factor, Ascl1, is sufficient to convert brain astrocytes into functional neurons, and GFAP-AAV is an efficient vector for generating iN cells from astrocytes in vivo.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yueguang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, State Key Laboratory of Cognitive Neuroscience and Learning, and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China, and University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Su'e
authors.initials: S
authors.lastname: Han
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Sanlan
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China, and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Junlan
authors.initials: J
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China, and lpcheng@ion.ac.cn xhzhang@bnu.edu.cn.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, University of Chinese Academy of Sciences, Shanghai 200031, China lpcheng@ion.ac.cn xhzhang@bnu.edu.cn.
authors.forename: Leping
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D000229:Dependovirus; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D060888:Real-Time Polymerase Chain Reaction; D014161:Transduction, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C499317:Ascl1 protein, mouse
keywords: astrocyte-to-neuron conversion in vivo; cell fate determination; induced neuronal (iN) cells; proneural gene Ascl1; transdifferentiation