作者
Gaia Colasante, Gabriele Lignani, Alicia Rubio, Lucian Medrihan, Latefa Yekhlef, Alessandro Sessa, Luca Massimino, Serena G Giannelli, Silvio Sacchetti, Massimiliano Caiazzo, Damiana Leo, Dimitra Alexopoulou, Maria Teresa Dell’Anno, Ernesto Ciabatti, Marta Orlando, Michele Studer, Andreas Dahl, Raul R Gainetdinov, Stefano Taverna, Fabio Benfenati, Vania Broccoli
发表日期
2015/12/3
期刊
Cell stem cell
卷号
17
期号
6
页码范围
719-734
出版商
Elsevier
简介
Transplantation of GABAergic interneurons (INs) can provide long-term functional benefits in animal models of epilepsy and other neurological disorders. Whereas GABAergic INs can be differentiated from embryonic stem cells, alternative sources of GABAergic INs may be more tractable for disease modeling and transplantation. We identified five factors (Foxg1, Sox2, Ascl1, Dlx5, and Lhx6) that convert mouse fibroblasts into induced GABAergic INs (iGABA-INs) possessing molecular signatures of telencephalic INs. Factor overexpression activates transcriptional networks required for GABAergic fate specification. iGABA-INs display progressively maturing firing patterns comparable to cortical INs, form functional synapses, and release GABA. Importantly, iGABA-INs survive and mature upon being grafted into mouse hippocampus. Optogenetic stimulation demonstrated functional integration of grafted iGABA-INs into …
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