Lineage-specific changes in mitochondrial properties during neural stem cell differentiation

• Published in: Life science alliance 2024-07, Vol.7 (7), p.e202302473
• Main Authors: Soares, Rita, Lourenço, Diogo, F. Mota, Isa, Sebastião, Ana M, Xapelli, Sara, Morais, Vanessa
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - cytology; Astrocytes - metabolism; Cell Differentiation - genetics; Cell Lineage - genetics; Cells, Cultured; Dynamins; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Lateral Ventricles - cytology; Lateral Ventricles - metabolism; Mice; Mitochondria - metabolism; Mitochondrial Dynamics; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Neurons - cytology; Neurons - metabolism; Oligodendroglia - cytology; Oligodendroglia - metabolism
• ISSN: 2575-1077; 2575-1077
• DOI: 10.26508/lsa.202302473

© 2024 Soares et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). Neural stem cells (NSCs) reside in discrete regions of the adult mammalian brain where they can differentiate into neurons, astrocytes, and oligodendrocytes. Several studies suggest that mitochondria have a major role in regulating NSC fate. Here, we evaluated mitochondrial properties throughout NSC differentiation and in lineage-specific cells. For this, we used the neurosphere assay model to isolate, expand, and differentiate mouse subventricular zone postnatal NSCs. We found that the levels of proteins involved in mitochondrial fusion (Mitofusin [Mfn] 1 and Mfn 2) increased, whereas proteins involved in fission (dynamin-related protein 1 [DRP1]) decreased along differentiation. Importantly, changes in mitochondrial dynamics correlated with distinct patterns of mitochondrial morphology in each lineage. Particularly, we found that the number of branched and unbranched mitochondria increased during astroglial and neuronal differentiation, whereas the area occupied by mitochondrial structures significantly reduced with oligodendrocyte maturation. In addition, comparing the three lineages, neurons revealed to be the most energetically flexible, whereas astrocytes presented the highest ATP content. Our work identified putative mitochondrial targets to enhance lineage-directed differentiation of mouse subventricular zone-derived NSCs. This work was supported by the European Molecular Biology Organization (EMBO), IG#3309; Fundação para a Ciência e Tecnologia (FCT) (PTDC/MED-NEU/7976/2020); International Society for Neurochemistry (ISN) Career Development Grant; and International Brain Research Organization (IBRO) Early Career Award. R Soares (PD/BD/128280/2017, COVID/BD/151619/2021, and IMM/BI/8-2021) and DM Lourenço (PD/BD/141784/2018 and COVID/BD/152658/2022) were in receipt of a fellowship from FCT. VA Morais is supported by FCT (IF/01693/2014; IMM/CT/27-2020). This project has received funding from H2020-WIDESPREAD-05-2020-Twinning (EpiEpinet) under grant agreement No 952455. We thank members of the VA Morais and AM Sebastião Labs for fruitful discussions. We would like to thank the BioImaging Facility, with a special thanks to José Rino, António Temudo, and Ana Nascimento and the Rodent Facility of Instituto de Medicina Molecular João Lobo Antunes for their technical support, and we a