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

Autor: Morello G; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy., Villari A; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy., Spampinato AG; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy., La Cognata V; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy., Guarnaccia M; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy., Gentile G; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy., Ciotti MT; Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Via E. Ramarini, 32, Monterotondo Scalo, 00015 Rome, Italy., Calissano P; European Brain Research Institute (EBRI Foundation), Viale Regina Elena, 295, 00161 Rome, Italy., D'Agata V; Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Via Santa Sofia, 87, 95123 Catania, Italy., Severini C; Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Via E. Ramarini, 32, Monterotondo Scalo, 00015 Rome, Italy., Cavallaro S; Institute for Biomedical Research and Innovation, National Research Council (IRIB-CNR), Via Paolo Gaifami, 18, 95125 Catania, Italy.
Jazyk: angličtina
Zdroj: Cells [Cells] 2021 Nov 19; Vol. 10 (11). Date of Electronic Publication: 2021 Nov 19.
DOI: 10.3390/cells10113238
Abstrakt: 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.
Databáze: MEDLINE
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