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A single-cell transcriptomic atlas of exercise-induced anti–inflammatory and geroprotective effects across the body

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A single-cell transcriptomic atlas of exercise-induced antiinammatory
and geroprotective effects across the body
Shuhui Sun, Shuai Ma, Yusheng Cai, Si Wang, Jie Ren, Yuanhan Yang, Jiale Ping, Xuebao Wang, Yiyuan Zhang, Haoteng Yan, Wei Li,
Concepcion Rodriguez Esteban, Yan Yu, Feifei Liu, Juan Carlos Izpisua Belmonte, Weiqi Zhang,*Jing Qu,*and Guang-Hui Liu*
*Correspondence: zhangwq@big.ac.cn (W.Z.); qujing@ioz.ac.cn (J.Q.); ghliu@ioz.ac.cn (G.-H.L.)
https://doi.org/10.1016/j.xinn.2025.100806
ª2025 Published by Elsevier Inc. on behalf of Youth Innovation Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Citation: Sun S., Ma S., Cai Y., et al., (2025). A single-cell transcriptomic atlas of exercise-induced antiinammatory and geroprotective effects across the body. The Innovation 6(2), 100806.
(The Innovation 4, 100380; January 30, 2023)
In the originally published version of this article, we, the authors, inadvertently included the wrong image for the aged
group in Figure 5A (spinal vGM column). This does not affect the discussions or conclusions of the paper, and we
deeply regret this oversight. The correct gure has been incorporated in the original paper online.
ll The Innovation 6(2): 100806, February 3, 2025 1
CORRECTION
AB C
D
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Figure 5. Exercise alleviates a panel of aging-associated phenotypes across tissues (corrected)
2The Innovation 6(2): 100806, February 3, 2025 www.cell.com/the-innovation
www.the-innovation.org
CORRECTION
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INTRODUCTION Physical exercise is a primary defense against age‐related cognitive decline and Alzheimer's disease (AD). METHODS We conducted single‐nucleus transcriptomic and chromatin accessibility analyses (snRNA‐seq and snATAC‐seq) on the hippocampus of mice carrying mutations in the amyloid precursor protein gene (APPNL‐G‐F) following prolonged voluntary wheel‐running exercise. RESULTS Exercise mitigates amyloid‐induced changes in transcriptome and chromatin accessibility through cell type–specific regulatory networks converging on growth factor signaling, particularly the epidermal growth factor receptor (EGFR) signaling. The beneficial effects of exercise on neurocognition can be blocked by pharmacological inhibition of EGFR and its downstream PI3K signaling. Exercise leads to elevated levels of heparin‐binding EGF (HB‐EGF), and intranasal administration of HB‐EGF enhances memory function in sedentary APPNL‐G‐F mice. DISCUSSION These findings offer a panoramic delineation of cell type–specific hippocampal transcriptional networks activated by exercise and suggest EGFR signaling as a druggable contributor to exercise‐induced memory enhancement to combat AD‐related cognitive decline. Highlights snRNA‐seq and snATAC‐seq analysis of APPNL‐G‐F mice after prolonged wheel‐running. Exercise counteracts amyloid‐induced transcriptomic and accessibility changes. Networks converge on the activation of EGFR and insulin signaling. Pharmacological inhibition of EGFR and PI3K blocked cognitive benefits of exercise. Intranasal HB‐EGF administration enhances memory in sedentary APPNL‐G‐F mice.
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