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

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 differ...

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Autores principales:	Giovanna Morello, Ambra Villari, Antonio Gianmaria Spampinato, Valentina La Cognata, Maria Guarnaccia, Giulia Gentile, Maria Teresa Ciotti, Pietro Calissano, Velia D’Agata, Cinzia Severini, Sebastiano Cavallaro
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	apoptosis neurotrophic factors survival transcriptional analysis drug targets drug repurposing Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bf4dceea56c040848861d39dfefd1ec4
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spelling	oai:doaj.org-article:bf4dceea56c040848861d39dfefd1ec42021-11-25T17:13:10ZTranscriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival10.3390/cells101132382073-4409https://doaj.org/article/bf4dceea56c040848861d39dfefd1ec42021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3238https://doaj.org/toc/2073-4409Neuronal 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.Giovanna MorelloAmbra VillariAntonio Gianmaria SpampinatoValentina La CognataMaria GuarnacciaGiulia GentileMaria Teresa CiottiPietro CalissanoVelia D’AgataCinzia SeveriniSebastiano CavallaroMDPI AGarticleapoptosisneurotrophic factorssurvivaltranscriptional analysisdrug targetsdrug repurposingBiology (General)QH301-705.5ENCells, Vol 10, Iss 3238, p 3238 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	apoptosis neurotrophic factors survival transcriptional analysis drug targets drug repurposing Biology (General) QH301-705.5
spellingShingle	apoptosis neurotrophic factors survival transcriptional analysis drug targets drug repurposing Biology (General) QH301-705.5 Giovanna Morello Ambra Villari Antonio Gianmaria Spampinato Valentina La Cognata Maria Guarnaccia Giulia Gentile Maria Teresa Ciotti Pietro Calissano Velia D’Agata Cinzia Severini Sebastiano Cavallaro Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival
description	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.
format	article
author	Giovanna Morello Ambra Villari Antonio Gianmaria Spampinato Valentina La Cognata Maria Guarnaccia Giulia Gentile Maria Teresa Ciotti Pietro Calissano Velia D’Agata Cinzia Severini Sebastiano Cavallaro
author_facet	Giovanna Morello Ambra Villari Antonio Gianmaria Spampinato Valentina La Cognata Maria Guarnaccia Giulia Gentile Maria Teresa Ciotti Pietro Calissano Velia D’Agata Cinzia Severini Sebastiano Cavallaro
author_sort	Giovanna Morello
title	Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival
title_short	Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival
title_full	Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival
title_fullStr	Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival
title_full_unstemmed	Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival
title_sort	transcriptional profiles of cell fate transitions reveal early drivers of neuronal apoptosis and survival
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bf4dceea56c040848861d39dfefd1ec4
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Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival

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