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Article

Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival

1
Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy
2
Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Via E. Ramarini, 32, Monterotondo Scalo, 00015 Rome, Italy
3
European Brain Research Institute (EBRI Foundation), Viale Regina Elena, 295, 00161 Rome, Italy
4
Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Via Santa Sofia, 87, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Naweed I. Syed
Cells 2021, 10(11), 3238; https://doi.org/10.3390/cells10113238
Received: 19 October 2021 / Revised: 12 November 2021 / Accepted: 17 November 2021 / Published: 19 November 2021
(This article belongs to the Special Issue Neurotrophic Factors in Health and Disease)
Neuronal apoptosis and survival are regulated at the transcriptional level. To identify key genes and upstream regulators primarily responsible for these processes, we overlayed the temporal transcriptome of cerebellar granule neurons following induction of apoptosis and their rescue by three different neurotrophic factors. We identified a core set of 175 genes showing opposite expression trends at the intersection of apoptosis and survival. Their functional annotations and expression signatures significantly correlated to neurological, psychiatric and oncological disorders. Transcription regulatory network analysis revealed the action of nine upstream transcription factors, converging pro-apoptosis and pro-survival-inducing signals in a highly interconnected functionally and temporally ordered manner. Five of these transcription factors are potential drug targets. Transcriptome-based computational drug repurposing produced a list of drug candidates that may revert the apoptotic core set signature. Besides elucidating early drivers of neuronal apoptosis and survival, our systems biology-based perspective paves the way to innovative pharmacology focused on upstream targets and regulatory networks.
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Keywords: apoptosis; neurotrophic factors; survival; transcriptional analysis; drug targets; drug repurposing; functional enrichment; regulatory network; disease apoptosis; neurotrophic factors; survival; transcriptional analysis; drug targets; drug repurposing; functional enrichment; regulatory network; disease
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MDPI and ACS Style

Morello, G.; Villari, A.; Spampinato, A.G.; La Cognata, V.; Guarnaccia, M.; Gentile, G.; Ciotti, M.T.; Calissano, P.; D’Agata, V.; Severini, C.; Cavallaro, S. Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival. Cells 2021, 10, 3238. https://doi.org/10.3390/cells10113238

AMA Style

Morello G, Villari A, Spampinato AG, La Cognata V, Guarnaccia M, Gentile G, Ciotti MT, Calissano P, D’Agata V, Severini C, Cavallaro S. Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival. Cells. 2021; 10(11):3238. https://doi.org/10.3390/cells10113238

Chicago/Turabian Style

Morello, Giovanna, Ambra Villari, Antonio G. Spampinato, Valentina La Cognata, Maria Guarnaccia, Giulia Gentile, Maria T. Ciotti, Pietro Calissano, Velia D’Agata, Cinzia Severini, and Sebastiano Cavallaro. 2021. "Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival" Cells 10, no. 11: 3238. https://doi.org/10.3390/cells10113238

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