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Integration of transcriptomics and metabolomics reveals pathways involved in MDSC supernatant attenuation of TGF-β1-induced myofibroblastic differentiation of mesenchymal stem cells

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Abstract

Overexposure to transforming growth factor b1 (TGF-β1) induces myofibroblastic differentiation of mesenchymal stem cells (MSCs), which could be attenuated by myeloid-derived suppressor cell (MDSC) supernatant. However, the promyofibroblastic effects of TGF-β1 and the antimyofibroblastic effects of MDSC supernatant in MSCs have not been fully elucidated. To further clarify the latent mechanism and identify underlying therapeutic targets, we used an integrative strategy combining transcriptomics and metabolomics. Bone marrow MSCs were collected 24 h following TGF-β1 and MDSC supernatant treatment for RNA sequencing and untargeted metabolomic analysis. The integrated data were then analyzed to identify significant gene-metabolite correlations. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) were assessed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for exploring the mechanisms of myofibroblastic differentiation of MSCs. The integration of transcriptomic and metabolomic data highlighted significantly coordinated changes in glycolysis/gluconeogenesis and purine metabolism following TGF-β1 and MDSC supernatant treatment. By combining transcriptomic and metabolomic analyses, this study showed that glycolysis/gluconeogenesis and purine metabolism were essential for the myofibroblastic differentiation of MSCs and may serve as promising targets for mechanistic research and clinical practice in the treatment of fibrosis by MDSC supernatant.

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Funding

This study was supported by the National Key R&D Program of China (2018YFA0107501) and National Natural Science Foundation of China (81770747 and 81970646).

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Author notes

  1. Yin Celeste Cheuk, Xinhao Niu and Yongxin Mao have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Yin Celeste Cheuk

  2. Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032, China

    Yin Celeste Cheuk, Xinhao Niu, Jiawei Li, Jiyan Wang, Shihao Xu, Yongsheng Luo, Xuanchuan Wang, Yi Zhang & Ruiming Rong

  3. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yin Celeste Cheuk, Xinhao Niu, Jiawei Li, Jiyan Wang, Shihao Xu, Yongsheng Luo, Xuanchuan Wang & Ruiming Rong

  4. Department of Urology, Huadong Hospital, Fudan University, Shanghai, 200040, China

    Yongxin Mao

  5. Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Weixi Wang

  6. Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yi Zhang

  7. Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China

    Shihao Xu

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  1. Yin Celeste Cheuk
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  2. Xinhao Niu
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  3. Yongxin Mao
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  9. Xuanchuan Wang
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  11. Ruiming Rong
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Correspondence to Xuanchuan Wang, Yi Zhang or Ruiming Rong.

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All protocols and use of laboratory animals were approved by Animal Ethics Committee of Zhongshan Hospital, Fudan University.

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Cheuk, Y.C., Niu, X., Mao, Y. et al. Integration of transcriptomics and metabolomics reveals pathways involved in MDSC supernatant attenuation of TGF-β1-induced myofibroblastic differentiation of mesenchymal stem cells. Cell Tissue Res 390, 465–489 (2022). https://doi.org/10.1007/s00441-022-03681-2

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