年龄和性别对基于基因表达的小鼠外周血辐射生物剂量测定的影响。

IF 1.7 4区 生物学 Q4 CELL BIOLOGY
Cytogenetic and Genome Research Pub Date : 2023-01-01 Epub Date: 2023-03-16 DOI:10.1159/000530172
Constantinos G Broustas, Igor Shuryak, Axel J Duval, Sally A Amundson
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引用次数: 0

摘要

可以重建辐射暴露的基于血液的基因表达谱正被开发为辐射生物剂量测定的一种实用方法。然而,年龄和性别可能会限制这种方法的准确性。在这项研究中,我们确定了年龄对暴露于辐射的雌性小鼠外周血细胞基因表达谱的影响,并确定了与先前获得的雄性小鼠转录组特征的差异和相似性。用4Gy X射线照射年轻(2个月)和年老(24个月)雌性小鼠,24小时后从血液中分离总RNA,并进行全基因组微阵列分析。使用在受辐射的年轻雄性小鼠的基因表达数据上训练的基因签名进行的剂量重建分析显示,在年轻雌性小鼠中,0或4 Gy剂量的准确重建具有±0.75 Gy(R^2=0.90)的均方根误差。尽管辐照的老年雌性小鼠的剂量重建不如年轻雌性小鼠准确,但与实际辐射剂量的偏差在统计学上并不显著。差异表达基因的通路分析显示,在年轻雌性小鼠的差异表达基因中,照射后,细胞凋亡相关功能过度表达,而与各种免疫细胞亚型数量相关的功能缺乏代表性,而老年动物则不然。此外,年轻小鼠显著上调了参与吞噬作用的基因,这一过程可以消除凋亡细胞并保持组织稳态。这两种功能在4 Gy X射线照射后的年轻雄性小鼠中也过多表达,但在老年雄性小鼠中没有。最后,与中性粒细胞激活相关的功能,对杀死入侵病原体和调节炎症反应至关重要,被预测在年轻而非老年雌性小鼠中独特富集。这项工作支持了这样一个概念,即可以在小鼠中识别外周血基因表达谱,从而准确预测物理辐射剂量暴露,而不考虑年龄和性别。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of Age and Sex on Gene Expression-Based Radiation Biodosimetry Using Mouse Peripheral Blood.

Blood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to radiation biodosimetry. However, age and sex could potentially limit the accuracy of the approach. In this study, we determined the impact of age on the peripheral blood cell gene expression profile of female mice exposed to radiation and identified differences and similarities with a previously obtained transcriptomic signature of male mice. Young (2 months) and old (24 months) female mice were irradiated with 4 Gy X-rays, total RNA was isolated from blood 24 hours later and subjected to whole-genome microarray analysis. Dose reconstruction analyses using a gene signature trained on gene expression data from irradiated young male mice showed accurate reconstruction of 0 or 4 Gy doses with root mean square error of ±0.75 Gy (R2 = 0.90) in young female mice. Although dose reconstruction for irradiated old female mice was less accurate than young female mice, the deviation from the actual radiation dose was not statistically significant. Pathway analysis of differentially expressed genes revealed that after irradiation, apoptosis-related functions were overrepresented, whereas functions related to quantities of various immune cell subtypes were underrepresented, among differentially expressed genes from young female mice, but not older animals. Furthermore, young mice significantly upregulated genes involved in phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. Both functions were also overrepresented in young, but not old, male mice following 4 Gy X-irradiation. Lastly, functions associated with neutrophil activation that is essential for killing invading pathogens and regulating the inflammatory response were predicted to be uniquely enriched in young but not old female mice. This work supports the concept that peripheral blood gene expression profiles can be identified in mice that accurately predict physical radiation dose exposure irrespective of age and sex.

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来源期刊
Cytogenetic and Genome Research
Cytogenetic and Genome Research 生物-细胞生物学
CiteScore
3.10
自引率
5.90%
发文量
25
审稿时长
1 months
期刊介绍: During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.
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