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疾病模型的全身体转录组图谱

The Body-wide Transcriptome Landscape of Disease Models.

作者信息

Kozawa Satoshi, Ueda Ryosuke, Urayama Kyoji, Sagawa Fumihiko, Endo Satsuki, Shiizaki Kazuhiro, Kurosu Hiroshi, Maria de Almeida Glicia, Hasan Sharif M, Nakazato Kiyokazu, Ozaki Shinji, Yamashita Yoshinori, Kuro-O Makoto, Sato Thomas N

机构信息

The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR), 2-2-2 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0288, Japan; ERATO Sato Live Bio-Forecasting Project, Japan Science and Technology Agency (JST), Kyoto 619-0288, Japan.

The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR), 2-2-2 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0288, Japan; ERATO Sato Live Bio-Forecasting Project, Japan Science and Technology Agency (JST), Kyoto 619-0288, Japan; Karydo TherapeutiX, Inc., Tokyo 102-0082, Japan.

出版信息

iScience. 2018 Apr 27;2:238-268. doi: 10.1016/j.isci.2018.03.014. Epub 2018 Mar 29.

Abstract

Virtually all diseases affect multiple organs. However, our knowledge of the body-wide effects remains limited. Here, we report the body-wide transcriptome landscape across 13-23 organs of mouse models of myocardial infarction, diabetes, kidney diseases, cancer, and pre-mature aging. Using such datasets, we find (1) differential gene expression in diverse organs across all models; (2) skin as a disease-sensor organ represented by disease-specific activities of putative gene-expression network; (3) a bone-skin cross talk mediated by a bone-derived hormone, FGF23, in response to dysregulated phosphate homeostasis, a known risk-factor for kidney diseases; (4) candidates for the signature activities of many more putative inter-organ cross talk for diseases; and (5) a cross-species map illustrating organ-to-organ and model-to-disease relationships between human and mouse. These findings demonstrate the usefulness and the potential of such body-wide datasets encompassing mouse models of diverse disease types as a resource in biological and medical sciences. Furthermore, the findings described herein could be exploited for designing disease diagnosis and treatment.

摘要

几乎所有疾病都会影响多个器官。然而,我们对其全身影响的了解仍然有限。在此,我们报告了心肌梗死、糖尿病、肾脏疾病、癌症和早衰小鼠模型的13 - 23个器官的全身转录组图谱。利用这些数据集,我们发现:(1)所有模型中不同器官的基因表达存在差异;(2)皮肤作为疾病传感器官,由假定基因表达网络的疾病特异性活动所代表;(3)在磷酸盐稳态失调(一种已知的肾脏疾病风险因素)的情况下,由骨源性激素FGF23介导的骨 - 皮肤相互作用;(4)更多假定的疾病器官间相互作用的标志性活动的候选因素;以及(5)一张跨物种图谱,展示了人类和小鼠之间器官与器官、模型与疾病的关系。这些发现证明了包含多种疾病类型小鼠模型的此类全身数据集作为生物和医学科学资源的实用性和潜力。此外,本文所述的发现可用于设计疾病诊断和治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb62/6135982/668383522a9d/fx1.jpg

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