Gene expression changes in male and female rhesus macaque 60 days after irradiation.

<h4>Purpose</h4>Transcriptome changes can be expected in survivors after lethal irradiation. We aimed to characterize these in males and females and after different cytokine treatments 60 days after irradiation.<h4>Material and methods</h4>Male and female rhesus macaques (n =...

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Autores principales:	Matthäus Majewski, Patrick Ostheim, Zoya Gluzman-Poltorak, Vladimir Vainstein, Lena Basile, Simone Schüle, Michael Haimerl, Christian Stroszczynski, Matthias Port, Michael Abend
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/391ff62d020e47c680a07b2a40068aa3
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spelling	oai:doaj.org-article:391ff62d020e47c680a07b2a40068aa32021-12-02T20:06:45ZGene expression changes in male and female rhesus macaque 60 days after irradiation.1932-620310.1371/journal.pone.0254344https://doaj.org/article/391ff62d020e47c680a07b2a40068aa32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254344https://doaj.org/toc/1932-6203<h4>Purpose</h4>Transcriptome changes can be expected in survivors after lethal irradiation. We aimed to characterize these in males and females and after different cytokine treatments 60 days after irradiation.<h4>Material and methods</h4>Male and female rhesus macaques (n = 142) received a whole-body exposure with 700 cGy, from which 60 animals survived. Peripheral whole blood was drawn pre-exposure and before sacrificing the surviving animals after 60 days.<h4>Results</h4>We evaluated gene expression in a three-phase study design. Phase I was a whole-genome screening (NGS) for mRNAs using five pre- and post-exposure RNA samples from both sexes (n = 20). Differential gene expression (DGE) was calculated between samples of survivors and pre-exposure samples (reference), separately for males and females. 1,243 up- and down-regulated genes were identified with 30-50% more deregulated genes in females. 37 candidate mRNAs were chosen for qRT-PCR validation in phase II using the remaining samples (n = 117). Altogether 17 genes showed (borderline) significant (t-test) DGE in groups of untreated or treated animals. Nine genes (CD248, EDAR, FAM19A5, GAL3ST4, GCNT4, HBG2/1, LRRN1, NOG, SYT14) remained with significant changes and were detected in at least 50% of samples per group. Panther analysis revealed an overlap between both sexes, related to the WNT signaling pathway, cell adhesion and immunological functions. For phase III, we validated the nine genes with candidate genes (n = 32) from an earlier conducted study on male baboons. Altogether 14 out of 41 genes showed a concordantly DGE across both species in a bilateral comparison.<h4>Conclusions</h4>Sixty days after radiation exposure, we identified (1) sex and cytokine treatment independent transcriptional changes, (2) females with almost twice as much deregulated genes appeared more radio-responsive than males, (3) Panther analysis revealed an association with immunological processes and WNT pathway for both sexes.Matthäus MajewskiPatrick OstheimZoya Gluzman-PoltorakVladimir VainsteinLena BasileSimone SchüleMichael HaimerlChristian StroszczynskiMatthias PortMichael AbendPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254344 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthäus Majewski Patrick Ostheim Zoya Gluzman-Poltorak Vladimir Vainstein Lena Basile Simone Schüle Michael Haimerl Christian Stroszczynski Matthias Port Michael Abend Gene expression changes in male and female rhesus macaque 60 days after irradiation.
description	<h4>Purpose</h4>Transcriptome changes can be expected in survivors after lethal irradiation. We aimed to characterize these in males and females and after different cytokine treatments 60 days after irradiation.<h4>Material and methods</h4>Male and female rhesus macaques (n = 142) received a whole-body exposure with 700 cGy, from which 60 animals survived. Peripheral whole blood was drawn pre-exposure and before sacrificing the surviving animals after 60 days.<h4>Results</h4>We evaluated gene expression in a three-phase study design. Phase I was a whole-genome screening (NGS) for mRNAs using five pre- and post-exposure RNA samples from both sexes (n = 20). Differential gene expression (DGE) was calculated between samples of survivors and pre-exposure samples (reference), separately for males and females. 1,243 up- and down-regulated genes were identified with 30-50% more deregulated genes in females. 37 candidate mRNAs were chosen for qRT-PCR validation in phase II using the remaining samples (n = 117). Altogether 17 genes showed (borderline) significant (t-test) DGE in groups of untreated or treated animals. Nine genes (CD248, EDAR, FAM19A5, GAL3ST4, GCNT4, HBG2/1, LRRN1, NOG, SYT14) remained with significant changes and were detected in at least 50% of samples per group. Panther analysis revealed an overlap between both sexes, related to the WNT signaling pathway, cell adhesion and immunological functions. For phase III, we validated the nine genes with candidate genes (n = 32) from an earlier conducted study on male baboons. Altogether 14 out of 41 genes showed a concordantly DGE across both species in a bilateral comparison.<h4>Conclusions</h4>Sixty days after radiation exposure, we identified (1) sex and cytokine treatment independent transcriptional changes, (2) females with almost twice as much deregulated genes appeared more radio-responsive than males, (3) Panther analysis revealed an association with immunological processes and WNT pathway for both sexes.
format	article
author	Matthäus Majewski Patrick Ostheim Zoya Gluzman-Poltorak Vladimir Vainstein Lena Basile Simone Schüle Michael Haimerl Christian Stroszczynski Matthias Port Michael Abend
author_facet	Matthäus Majewski Patrick Ostheim Zoya Gluzman-Poltorak Vladimir Vainstein Lena Basile Simone Schüle Michael Haimerl Christian Stroszczynski Matthias Port Michael Abend
author_sort	Matthäus Majewski
title	Gene expression changes in male and female rhesus macaque 60 days after irradiation.
title_short	Gene expression changes in male and female rhesus macaque 60 days after irradiation.
title_full	Gene expression changes in male and female rhesus macaque 60 days after irradiation.
title_fullStr	Gene expression changes in male and female rhesus macaque 60 days after irradiation.
title_full_unstemmed	Gene expression changes in male and female rhesus macaque 60 days after irradiation.
title_sort	gene expression changes in male and female rhesus macaque 60 days after irradiation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/391ff62d020e47c680a07b2a40068aa3
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Gene expression changes in male and female rhesus macaque 60 days after irradiation.

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