| Title: |
Transcriptomic and metabolic signatures of neural cells cultured under a physiologic-like environment |
| Authors: |
Fernández, Emilio; Warde, Moussa; Manjarrés-Raza, Israel; Bobo-Jimenez, Veronica; Martinez-Luna, Maria; Vicente-Gutiérrez, Carlos; Garcia-Rodriguez, Dario; Jimenez-Blasco, Daniel; Almeida, Angeles; Bolaños, Juan P. |
| Contributors: |
Agencia Estatal de Investigación (España); Ministerio de Ciencia, Innovación y Universidades (España); Ministerio de Ciencia e Innovación (España); European Commission; Fundación la Caixa; Instituto de Salud Carlos III; Junta de Castilla y León; Consejo Superior de Investigaciones Científicas https://ror.org/02gfc7t72 |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2024 |
| Collection: |
Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| Subject Terms: |
Astrocyte; Energy metabolism; Glycolysis; Hypoxia; Neuron; Transcriptomics |
| Description: |
Cultured brain cells are used conventionally to investigate fundamental neurobiology and identify therapeutic targets against neural diseases. However, standard culture conditions do not simulate the natural cell microenvironment, thus hampering in vivo translational insight. Major weaknesses include atmospheric (21%) O2 tension and lack of intercellular communication, the two factors likely impacting metabolism and signaling. Here, we addressed this issue in mouse neurons and astrocytes in primary culture. We found that the signs of cellular and mitochondrial integrity were optimal when these cells were acclimated to grow in coculture, to emulate intercellular coupling, under physiologic (5%) O2 tension. Transcriptomic scrutiny, performed to elucidate the adaptive mechanism involved, revealed that the vast majority of differentially expressed transcripts were downregulated in both astrocytes and neurons. Gene ontology evaluation unveiled that the largest group of altered transcripts was glycolysis, which was experimentally validated by metabolic flux analyses. This protocol and database resource for neural cells grown under in vivo-like microenvironment may move forward the translation of basic into applied neurobiological research. ; The projects that gave rise to these results were funded by MICIU/AEI (PID2022–138813OB-I00, PID2019–105699RB-I00/10.13039/501100011033 and FEDER, UE to J. P. B.; SAF2017–90794-REDT to A. A.), la Caixa Foundation (grant agreement LCF/PR/HR23/52430016 to J. P. B.), Instituto de Salud Carlos III (CB16/10/00282 to J. P. B.; PI21/00727, RD16/0019/0018, PMP22/00084 to A. A.), Junta de Castilla y León (CSI011P23 and Escalera de Excelencia CLU-2017–03 to J. P. B. and A. A.) and the European Union’s Horizon Europe research and innovation program under the MSCA Doctoral Networks 2021 (101072759; FuEl ThE bRaiN In healtThY aging and age-related diseases, ETERNITY; to J. P. B. and A. A.). Estefanía Prieto-García was a recipient of a position by the Fondo Social Europeo, Youth Employment ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
#PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138813OB-I00/ES/IMPACTO DEL METABOLISMO DE LOS ASTROCITOS SOBRE LA REGULACION EPIGENETICA DE LAS FUNCIONES NEURALES DURANTE EL DETERIORO COGNITIVO/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105699RB-I00/ES/IMPACTO DE LA REPROGRAMACION METABOLICA DE LOS ASTROCITOS SOBRE LA FUNCION NEURONAL IN VIVO EN SALUD Y ENFERMEDAD/; info:eu-repo/grantAgreement/EC/HE/101072759; The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.jbc.2024.107937; https://doi.org/10.1016/j.jbc.2024.107937; Sí; Journal of Biological Chemistry 300(12): 107937 (2024); https://hdl.handle.net/10261/379114; http://dx.doi.org/10.13039/501100004837; http://dx.doi.org/10.13039/501100011033; http://dx.doi.org/10.13039/501100000780; http://dx.doi.org/10.13039/501100004587; http://dx.doi.org/10.13039/501100014180; https://api.elsevier.com/content/abstract/scopus_id/85209068245 |
| DOI: |
10.1016/j.jbc.2024.107937 |
| DOI: |
10.13039/501100004837 |
| DOI: |
10.13039/501100011033 |
| DOI: |
10.13039/501100000780 |
| DOI: |
10.13039/501100004587 |
| DOI: |
10.13039/501100014180 |
| Availability: |
https://hdl.handle.net/10261/379114; https://doi.org/10.1016/j.jbc.2024.107937; https://doi.org/10.13039/501100004837; https://doi.org/10.13039/501100011033; https://doi.org/10.13039/501100000780; https://doi.org/10.13039/501100004587; https://doi.org/10.13039/501100014180; https://api.elsevier.com/content/abstract/scopus_id/85209068245 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8570C285 |
| Database: |
BASE |