Péron, SophieMiyakoshi, Leo M.Brill, Monika S.Manzano Franco, DianaSerrano López, JuliaFan, WenqiangMarichal, NicolásGhanem, AlexanderConzelmann, Karl-KlausKarow, MarisaOrtega De La O, FelipeGascón Jiménez, SergioBerninger, Benedikt2024-05-202024-05-202023-12-12Sophie Péron, Leo M. Miyakoshi, Monika S. Brill, Diana Manzano-Franco, Julia Serrano-López, Wenqiang Fan, Nicolás Marichal, Alexander Ghanem, Karl-Klaus Conzelmann, Marisa Karow, Felipe Ortega, Sergio Gascón, Benedikt Berninger, Programming of neural progenitors of the adult subependymal zone towards a glutamatergic neuron lineage by neurogenin 2, Stem Cell Reports, Volume 18, Issue 12, 2023, pp. 2418-2433, https://doi.org/10.1016/j.stemcr.2023.10.019.10.1016/j.stemcr.2023.10.019https://hdl.handle.net/20.500.14352/104218Author contributions: S.P., L.M.M. and M.S.B. designed and performed experiments, interpreted and analyzed results, and wrote the manuscript. F.O., M.K., N.M., and W.F. designed and performed experiments. A.G. and K.-K.C. provided essential reagents. S.G. conceptualized, designed, and performed experiments; interpreted and analyzed results; and wrote the manuscript. B.B. conceptualized the study and experiments, interpreted results, and wrote the manuscript. All authors discussed the manuscript. UCM-Santander: CT82/20-CT83/20 Programa Ramón y Cajal: RYC-2015-19185 Ministerio de Ciencia e Innovación (MICINN): RTI2018-099345-B-I00 ; PID2021-128796OB-I00 ; PID2019-109155RB-I00 ; BFU2015-70067REDCAlthough adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a glutamatergic fate. Retrovirus-mediated expression of Neurog2 induced the glutamatergic lineage markers TBR2 and TBR1 in cultured SEZ progenitors, which differentiated into functional glutamatergic neurons. Likewise, Neurog2-transduced SEZ progenitors acquired glutamatergic neuron hallmarks in vivo. Intriguingly, they failed to migrate toward the olfactory bulb and instead differentiated within the SEZ or the adjacent striatum, where they received connections from local neurons, as indicated by rabies virus-mediated monosynaptic tracing. In contrast, lentivirus-mediated expression of Neurog2 failed to reprogram early SEZ neurons, which maintained GABAergic identity and migrated to the olfactory bulb. Our data show that NEUROG2 can program SEZ progenitors toward a glutamatergic identity but fails to reprogram their neuronal progeny.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article2213-6711https://doi.org/10.1016/j.stemcr.2023.10.01937995703https://www.sciencedirect.com/science/article/pii/S2213671123004216?via%3Dihubopen access577.1/2Adult neurogenesisNeural specificationNeural stem cellNeurogenin 2Adult subventricular zoneOlfactory bulbFate reprogrammingProneural geneBioquímica (Biología)Biología molecular (Biología)2403 Bioquímica