title: In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model.
abstract: Loss of neurons after brain injury and in neurodegenerative disease is often accompanied by reactive gliosis and scarring, which are difficult to reverse with existing treatment approaches. Here, we show that reactive glial cells in the cortex of stab-injured or Alzheimer's disease (AD) model mice can be directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1. Following expression of NeuroD1, astrocytes were reprogrammed into glutamatergic neurons, while NG2 cells were reprogrammed into glutamatergic and GABAergic neurons. Cortical slice recordings revealed both spontaneous and evoked synaptic responses in NeuroD1-converted neurons, suggesting that they integrated into local neural circuits. NeuroD1 expression was also able to reprogram cultured human cortical astrocytes into functional neurons. Our studies therefore suggest that direct reprogramming of reactive glial cells into functional neurons in vivo could provide an alternative approach for repair of injured or diseased brain.
authors.affiliation: Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: gongchen@psu.edu.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001930:Brain Injuries / Q000473:pathology*; D065150:Cellular Reprogramming; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000378:metabolism / Q000473:pathology; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D005971:Glutamates; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C093564:Neurogenic differentiation factor 1