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Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8

Author

Listed:
  • Nadège Hertzog

    (Johannes Gutenberg University Mainz
    University of Fribourg)

  • Mert Duman

    (Johannes Gutenberg University Mainz
    University of Fribourg)

  • Maëlle Bochud

    (University of Fribourg)

  • Valérie Brügger-Verdon

    (University of Fribourg)

  • Maren Gerhards

    (Johannes Gutenberg University Mainz)

  • Felicia Schön

    (Johannes Gutenberg University Mainz)

  • Franka Dorndecker

    (Johannes Gutenberg University Mainz)

  • Dies Meijer

    (University of Edinburgh)

  • Robert Fledrich

    (University of Leipzig)

  • Ruth Stassart

    (University of Leipzig)

  • Devanarayanan Siva Sankar

    (University of Fribourg)

  • Jörn Dengjel

    (University of Fribourg)

  • Sofía Raigón López

    (Johannes Gutenberg University Mainz)

  • Claire Jacob

    (Johannes Gutenberg University Mainz
    University of Fribourg)

Abstract

After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery. We found that HDAC8 is specifically expressed in sensory SCs and regulates the E3 ubiquitin ligase TRAF7, which destabilizes hypoxia-inducible factor 1-alpha (HIF1α) and counteracts the phosphorylation and upregulation of c-Jun, a major inducer of the repair SC phenotype. Our study indicates that this phenotype switch is regulated by different mechanisms in sensory and motor SCs and is accelerated by HDAC8 downregulation, which promotes sensory axon regeneration and sensory function recovery.

Suggested Citation

  • Nadège Hertzog & Mert Duman & Maëlle Bochud & Valérie Brügger-Verdon & Maren Gerhards & Felicia Schön & Franka Dorndecker & Dies Meijer & Robert Fledrich & Ruth Stassart & Devanarayanan Siva Sankar & , 2025. "Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55835-9
    DOI: 10.1038/s41467-025-55835-9
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    References listed on IDEAS

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    1. Stéphanie Kaeser-Pebernard & Christine Vionnet & Muriel Mari & Devanarayanan Siva Sankar & Zehan Hu & Carole Roubaty & Esther Martínez-Martínez & Huiyuan Zhao & Miguel Spuch-Calvar & Alke Petri-Fink &, 2022. "mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Matthew A. Deardorff & Masashige Bando & Ryuichiro Nakato & Erwan Watrin & Takehiko Itoh & Masashi Minamino & Katsuya Saitoh & Makiko Komata & Yuki Katou & Dinah Clark & Kathryn E. Cole & Elfride De B, 2012. "HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle," Nature, Nature, vol. 489(7415), pages 313-317, September.
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