title: An interneuron progenitor maintains neurogenic potential in vivo and differentiates into GABAergic interneurons after transplantation in the postnatal rat brain.
abstract: Dysfunction of cortical GABAergic interneurons are involved in numerous neurological disorders including epilepsy, schizophrenia and autism; and replenishment of these cells by transplantation strategy has proven to be a feasible and effective method to help revert the symptoms in several animal models. To develop methodology of generating transplantable GABAergic interneurons for therapy, we previously reported the isolation of a v-myc-induced GABAergic interneuron progenitor clone GE6 from embryonic ganglionic eminence (GE). These cells can proliferate and form functional inhibitory synapses in culture. Here, we tested their differentiation behavior in vivo by transplanting them into the postnatal rat forebrain. We found that GE6 cells migrate extensively in the neonatal forebrain and differentiate into both neurons and glia, but preferentially into neurons when compared with a sister progenitor clone CTX8. The neurogenic potential of GE6 cells is also maintained after transplantation into a non-permissive environment such as adult cortex or when treated with inflammatory cytokine in culture. The GE6-derived neurons were able to mature in vivo as GABAergic interneurons expressing GABAergic, not glutamatergic, presynaptic puncta. Finally, we propose that v-myc-induced human interneuron progenitor clones could be an alternative cell source of transplantable GABAergic interneurons for treating related neurological diseases in future clinic.
authors.affiliation: West China Developmental &Stem Cell Institute, Department of Obstetric &Gynecologic and Pediatric, Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Peiwei
authors.initials: P
authors.lastname: Hong
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Yuntian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: West China Developmental &Stem Cell Institute, Department of Obstetric &Gynecologic and Pediatric, Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: West China Developmental &Stem Cell Institute, Department of Obstetric &Gynecologic and Pediatric, Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.affiliation: West China Developmental &Stem Cell Institute, Department of Obstetric &Gynecologic and Pediatric, Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, P.R. China.
authors.forename: Hedong
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004622:Embryo, Mammalian; D015870:Gene Expression; D016259:Genes, myc; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D008473:Median Eminence / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D005680:gamma-Aminobutyric Acid