Dataset Information

The exploration of brain-body interactions of brain injury reveals organ-specific and diverse signatures

ABSTRACT: The importance of brain-body interactions in the progresses of diseases are increasingly noticed, and understanding the associated processes could vastly improve the health of whole organism. A comprehensive, whole-organism analysis of organ dynamics to identify the molecular processes within and between organs after brain injury caused by ischemic stroke has been lacking. Mice models of 24 hours ischemic brain injury are constructed. Proteomics and metabolomics are used to detect the changes of organ’s proteome and metaboleome, respectively, and multiple bioinformatics analysis are performed to investigate the changing signatures across organs after stroke. Then, the organ proteomics data combined with aging mouse organ transcriptome data and mouse organ scRNA-seq data to reveal the biological age of organs and cellular resource of differentially expressed proteins (DEPs) of organs after stroke, respectively. Finally, we cross-referenced stroke-related DEPs in plasma with their corresponding protein expression in each organ to investigate the original source of plasma proteins by using spearman’s correlation analysis. Bioinformatics analysis showing the synchronization and asynchronization of the stroke-related proteins involved in multiple regulatory pathways are universally across organs. Although significant inter-organ correlations exist without influenced by stroke, the protein expression changes may better reflect the inter-organ correlation after brain injury by sharing some common changing signatures. Then, hundreds of DEPs in organs with the greatest numbers of DEPs are revealed in heart, and they are unique and common expressed between organs. Notably, an integrate analysis of these DEPs with mouse aging RNA-seq data reveal ageing-like changes in organs, suggesting increased biological ages of organs. Furthermore, a conjoint analysis of our proteomic data with scRNA-seq data confirms the cellular source of DEPs originated from intrinsic cells and immune cells, and the latter are widely located and activated in organs. Finally, we find that some DEPs in plasma are highly correlated with corresponding protein levels in distinct organs, potentially resulting in the stroke of the systemic circulation. Together, this study demonstrates a similar yet asynchronous inter- and intra-organ progression of stroke, providing a fundamental resource for understanding the molecular mechanisms underlying brain-body interaction and potential interventions for brain injury.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, Heart, Brain, Blood Plasma, Intestine, Lung, Liver, Kidney

DISEASE(S): Cerebrovascular Disease

SUBMITTER: Yuanhong Deng

LAB HEAD: Yuanhong Deng

PROVIDER: PXD055505 | Pride | 2025-08-25

REPOSITORIES: Pride

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Integrated omics identifies molecular networks of brain-body interactions of brain injury.

Deng Yuan-Hong YH Wang Hong H Zhang Jia-Hang JH Wang Yu-Fei YF Wang Meng-Yao MY Pan Xin-Ru XR Zhang Yao-Dan YD Gan Yuan-Hui YH He Yi Y Xie Fang F Feng Xiao-Shuang XS Xie Jia-Xin JX Liu Bai-Tong BT Wang Jiang-Tao JT Zhang Xin-Xiao XX Wang Peng-Fei PF Li Jie J Yu Shu-Guang SG Yang Qing-Wu QW Bai Ming-Ze MZ Tang Yong Y Xiong Xiao-Yi XY

iScience 20250712 8

The molecular mechanisms of brain-body interactions in the progression of brain diseases remain unknown. Through integrative analysis of multi-organ proteomic, metabolomic, and transcriptomic data following ischemic stroke, we identified dynamic molecular signatures across organs. The heart exhibited the highest number of differentially expressed proteins (DEPs), followed by spleen and intestine. Ten DEPs were shared among three organs post-stroke, with eight in heart, six in spleen, and five in ...[more]

PMID: 40761293

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