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

Autor: Patrick Ostheim, Zoya Gluzman-Poltorak, Simone Schüle, Lena A. Basile, Michael Abend, Matthias Port, Christian Stroszczynski, Matthäus Majewski, Michael Haimerl, Vladimir Vainstein
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Candidate gene
Physiology
Gene Expression
Monkeys
Macaque
Transcriptome
0302 clinical medicine
Baboons
Cell Signaling
Immune Physiology
Gene expression
Medicine and Health Sciences
Membrane Receptor Signaling
Immune Response
Mammals
Regulation of gene expression
Innate Immune System
Multidisciplinary
biology
Wnt signaling pathway
Eukaryota
Animal Models
Radiation Injuries
Experimental
Rhesus macaque
Experimental Organism Systems
030220 oncology & carcinogenesis
Vertebrates
Medicine
Cytokines
Female
Whole-Body Irradiation
Research Article
Signal Transduction
Primates
Science
Immunology
Research and Analysis Methods
Andrology
03 medical and health sciences
biology.animal
Old World monkeys
Genetics
Animals
Gene Regulation
Gene
Rhesus Monkeys
Organisms
Biology and Life Sciences
Cell Biology
Molecular Development
biology.organism_classification
Macaca mulatta
030104 developmental biology
Gene Expression Regulation
Immune System
Amniotes
Animal Studies
Zoology
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 7, p e0254344 (2021)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0254344
Popis: Purpose 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. Material and methods 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. Results 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. Conclusions 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.
Databáze: OpenAIRE
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