1. Neural stem cells in the adult olfactory bulb core generate mature neurons in vivo
- Author
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Eva Díaz-Guerra, Eva Vergaño-Vera, Antonella Consiglio, Mireia Moreno-Estellés, Vanesa Nieto-Estévez, Çağla Defteralı, Carlos Crespo, Anahí Hurtado-Chong, Helena Mira, María Díaz-Moreno, Carlos Vicario, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, Generalitat Valenciana, European Research Council, Instituto de Salud Carlos III, Vicario-Abejón, Carlos, Mira, Helena, Vicario-Abejón, Carlos [0000-0002-7060-0250], and Mira, Helena [0000-0001-8574-9544]
- Subjects
0301 basic medicine ,Neurobiologia del desenvolupament ,Rostral migratory stream ,Neurogenesis ,Subventricular zone ,Stem cells ,Adult neurogenesis ,03 medical and health sciences ,Mice ,Olfactory bulb ,0302 clinical medicine ,Calretinin ,Neural Stem Cells ,Interneurons ,medicine ,Animals ,Developmental neurobiology ,Neural stem cells ,Neurons ,biology ,Cell Differentiation ,Cell Biology ,Olfactory Bulb ,Neural stem cell ,Doublecortin ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Synapses ,biology.protein ,Molecular Medicine ,Neuron ,NeuN ,Cèl·lules mare ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
17 páginas, 7 figuras., Although previous studies suggest that neural stem cells (NSCs) exist in the adult olfactory bulb (OB), their location, identity, and capacity to generate mature neurons in vivo has been little explored. Here, we injected enhanced green fluorescent protein (EGFP)-expressing retroviral particles into the OB core of adult mice to label dividing cells and to track the differentiation/maturation of any neurons they might generate. EGFP-labeled cells initially expressed adult NSC markers on days 1 to 3 postinjection (dpi), including Nestin, GLAST, Sox2, Prominin-1, and GFAP. EGFP+ -doublecortin (DCX) cells with a migratory morphology were also detected and their abundance increased over a 7-day period. Furthermore, EGFP-labeled cells progressively became NeuN+ neurons, they acquired neuronal morphologies, and they became immunoreactive for OB neuron subtype markers, the most abundant representing calretinin expressing interneurons. OB-NSCs also generated glial cells, suggesting they could be multipotent in vivo. Significantly, the newly generated neurons established and received synaptic contacts, and they expressed presynaptic proteins and the transcription factor pCREB. By contrast, when the retroviral particles were injected into the subventricular zone (SVZ), nearly all (98%) EGFP+ -cells were postmitotic when they reached the OB core, implying that the vast majority of proliferating cells present in the OB are not derived from the SVZ. Furthermore, we detected slowly dividing label-retaining cells in this region that could correspond to the population of resident NSCs. This is the first time NSCs located in the adult OB core have been shown to generate neurons that incorporate into OB circuits in vivo., This work was funded by grants from the Spanish “Ministerio de Economía y Competitividad and Ministerio de Ciencia, Innovacion y Universidades ” (MINECO and MICIU: SAF2013-4759R and SAF2016-80419-R, PID2019-109059RB-I00 to C.V., SAF2015-70433-R to H.M., BFU2016-80870-P to A.C., and CIBERNED CB06/05/0065 to C.V.), from the “Comunidad de Madrid” (S2011/BMD-2336) to C.V. and H.M., from the “Generalitat Valenciana” (PROMETEO/2018/055) to H.M., and from the CSIC Intramural program (Refs. 201220E098 and 201320E054) to C.V. Additional support was provided by the European Research Council (ERC) 2012-StG (311736-PD-HUMMODEL), the Instituto de Salud Carlos III - ISCIII/FEDER (Red de Terapia Celular - TerCel RD16/0011/0024 and PIE14/00061) to A.C. Ç.D. received a short-term fellowship from the Red Olfativa Española (ROE). M.M.-E, M.D.-M., A.H.-C., and V.N.-E. were supported by FPI Fellowships from the MICINN and MINECO.
- Published
- 2020