非人灵长类动物季节性转录组图谱揭示了生理和疾病的季节性变化。

Non-human primate seasonal transcriptome atlas reveals seasonal changes in physiology and diseases.

作者信息

Chen Junfeng, Okimura Kousuke, Ren Liang, Nakane Yusuke, Nakayama Tomoya, Chen Yang, Fukawa Kai, Sugiyama Soutarou, Natsume Takayoshi, Suda-Hashimoto Naoko, Morimoto Mayumi, Miyabe-Nishiwaki Takako, Oishi Takao, Katada Yuma, Zhang Manhui, Kobayashi Kohei, Matsumoto Shoko, Yamaguchi Taiki, Guh Ying-Jey, Takahashi Issey, Nishiwaki-Ohkawa Taeko, Sato Daiki X, Murata Yoshiharu, Sumiyama Kenta, Nagano Atsushi J, Imai Hiroo, Yoshimura Takashi

机构信息

Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Nagoya, Aichi, 464-8601, Japan.

Laboratory of Animal Integrative Physiology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan.

出版信息

Nat Commun. 2025 Apr 28;16(1):3906. doi: 10.1038/s41467-025-57994-1.

DOI:10.1038/s41467-025-57994-1

PMID:40295482

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12037758/

Abstract

The metabolic, immune, and endocrine systems show profound seasonal changes in animals, including humans. In addition, morbidity from cardiovascular and psychiatric diseases is more severe and mortality rate is higher in winter. However, their molecular mechanisms remain unknown. Here we report the seasonal transcriptome of 80 tissues collected over 1 year from male and female rhesus macaques kept in a semi-natural outdoor environment. We find seasonal changes in plasma metabolites and hormones. Transcriptome analysis identifies sex differences in seasonally oscillating genes (SOGs) in all tissues studied, and we generate the web database 'Non-Human Primate Seasonal Transcriptome Atlas (NHPSTA).' Transcriptional regulatory network analysis, siRNA knockdown, and mutant mouse analyses reveal regulation of SOGs by GA-binding protein (GABP). We also demonstrate seasonal oscillations in the expression of disease risk factor genes and drug interacting genes. NHPSTA provides a molecular resource for seasonally regulated physiology and targets for therapeutic interventions for seasonally regulated diseases.

摘要

代谢、免疫和内分泌系统在包括人类在内的动物中呈现出显著的季节性变化。此外，心血管疾病和精神疾病的发病率在冬季更为严重，死亡率也更高。然而，它们的分子机制仍然未知。在此，我们报告了从生活在半自然户外环境中的雄性和雌性恒河猴身上，在一年时间里收集的80种组织的季节性转录组。我们发现了血浆代谢物和激素的季节性变化。转录组分析确定了所有研究组织中季节性振荡基因（SOGs）的性别差异，并且我们创建了网络数据库“非人灵长类动物季节性转录组图谱（NHPSTA）”。转录调控网络分析、小干扰RNA敲低和突变小鼠分析揭示了GA结合蛋白（GABP）对SOGs的调控作用。我们还证明了疾病风险因子基因和药物相互作用基因表达的季节性振荡。NHPSTA为季节性调节的生理学提供了分子资源，并为季节性调节疾病的治疗干预提供了靶点。