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Synergic Functions of miRNAs Determine Neuronal Fate of Adult Neural Stem Cells

Adult neurogenesis requires the precise control of neuronal versus astrocyte lineage determination in neural stem cells. While microRNAs (miRNAs) are critically involved in this step during development, their actions in adult hippocampal neural stem cells (aNSCs) has been unclear. As entry point to...

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Detalles Bibliográficos
Autores principales: Pons-Espinal, Meritxell, de Luca, Emanuela, Marzi, Matteo Jacopo, Beckervordersandforth, Ruth, Armirotti, Andrea, Nicassio, Francesco, Fabel, Klaus, Kempermann, Gerd, De Pietri Tonelli, Davide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390108/
https://www.ncbi.nlm.nih.gov/pubmed/28330621
http://dx.doi.org/10.1016/j.stemcr.2017.02.012
Descripción
Sumario:Adult neurogenesis requires the precise control of neuronal versus astrocyte lineage determination in neural stem cells. While microRNAs (miRNAs) are critically involved in this step during development, their actions in adult hippocampal neural stem cells (aNSCs) has been unclear. As entry point to address that question we chose DICER, an endoribonuclease essential for miRNA biogenesis and other RNAi-related processes. By specific ablation of Dicer in aNSCs in vivo and in vitro, we demonstrate that miRNAs are required for the generation of new neurons, but not astrocytes, in the adult murine hippocampus. Moreover, we identify 11 miRNAs, of which 9 have not been previously characterized in neurogenesis, that determine neurogenic lineage fate choice of aNSCs at the expense of astrogliogenesis. Finally, we propose that the 11 miRNAs sustain adult hippocampal neurogenesis through synergistic modulation of 26 putative targets from different pathways.