title: In vivo conversion of astrocytes to neurons in the injured adult spinal cord.
abstract: Spinal cord injury (SCI) leads to irreversible neuronal loss and glial scar formation, which ultimately result in persistent neurological dysfunction. Cellular regeneration could be an ideal approach to replenish the lost cells and repair the damage. However, the adult spinal cord has limited ability to produce new neurons. Here we show that resident astrocytes can be converted to doublecortin (DCX)-positive neuroblasts by a single transcription factor, SOX2, in the injured adult spinal cord. Importantly, these induced neuroblasts can mature into synapse-forming neurons in vivo. Neuronal maturation is further promoted by treatment with a histone deacetylase inhibitor, valproic acid (VPA). The results of this study indicate that in situ reprogramming of endogenous astrocytes to neurons might be a potential strategy for cellular regeneration after SCI.
authors.affiliation: 1] Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA [2] Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, 800 Xiangyin Rd, Shanghai 200433, China.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.
authors.forename: Wenze
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.
authors.forename: Meng-Lu
authors.initials: ML
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D019556:COS Cells; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D000089662:Doublecortin Protein; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014162:Transfection / Q000379:methods
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D055748:SOXB1 Transcription Factors; D049452:Green Fluorescent Proteins