Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury

Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury View ORCID Profile E. Stepanova , View ORCID Profile S. Hunter-Chang , J. Lee , A. Tripathi , View ORCID Profile C. Pavelec , C Cho , T. Vegiraju , J. Guo , C. Kim-Aun , View ORCID Profile S. Kucenas , View ORCID Profile N. Leitinger , View ORCID Profile J. Coutinho-Budd , View ORCID Profile J. Campbell , C. Deppmann doi: https://doi.org/10.1101/2024.07.11.603162 E. Stepanova 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America 6 Program in Fundamental Neuroscience, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for E. Stepanova S. Hunter-Chang 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America 2 Neuroscience Graduate Program, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for S. Hunter-Chang J. Lee 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site A. Tripathi 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site C. Pavelec 7 Department of Pharmacology, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 8 Robert M. Berne Cardiovascular Research Center, School of Medicine, University of Virginia , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for C. Pavelec C Cho 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site T. Vegiraju 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site J. Guo 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site C. Kim-Aun 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site S. Kucenas 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America 2 Neuroscience Graduate Program, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 4 Department of Neuroscience, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 6 Program in Fundamental Neuroscience, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for S. Kucenas N. Leitinger 7 Department of Pharmacology, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 8 Robert M. Berne Cardiovascular Research Center, School of Medicine, University of Virginia , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for N. Leitinger J. Coutinho-Budd 2 Neuroscience Graduate Program, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 4 Department of Neuroscience, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 6 Program in Fundamental Neuroscience, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for J. Coutinho-Budd J. Campbell 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America 2 Neuroscience Graduate Program, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 6 Program in Fundamental Neuroscience, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for J. Campbell For correspondence: jnc4e{at}virginia.edu deppmann{at}virginia.edu C. Deppmann 1 Department of Biology, College of Arts and Sciences , Charlottesville, VA 22902, United States of America 2 Neuroscience Graduate Program, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 3 Department of Biomedical Engineering, School of Engineering, University of Virginia , Charlottesville, VA 22902, United States of America 4 Department of Neuroscience, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 5 Department of Cell Biology, School of Medicine, University of Virginia , Charlottesville, VA 229022, United States of America 6 Program in Fundamental Neuroscience, College of Arts and Sciences , Charlottesville, VA 22902, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: jnc4e{at}virginia.edu deppmann{at}virginia.edu Abstract Full Text Info/History Metrics Preview PDF Abstract Schwann cells (SCs) transition into a Repair state after peripheral nerve injury; however, the early SC injury response preceding this transition remains poorly understood. We demonstrate that Sarm1, a key regulator of axon degeneration, is expressed and upregulated in SCs after nerve injury. Cell-type-specific Sarm1 knockout SCs exhibit enhanced axon protection in vitro , and SC- and glia-specific Sarm1 deletion confers axon protection in mouse sciatic nerve and Drosophila wing injury models. Single-nucleus RNA sequencing revealed that Sarm1-deficient SCs are enriched in a distinct cluster expressing genes with developmental roles in axon and myelin protection, with increased oxidative phosphorylation gene expression across all injured SC states. We propose that Sarm1 gates the transition from a Protection-Associated Schwann Cell (PASC) state to a Repair SC state, establishing Sarm1 as a multi-functional regulator with implications for peripheral neuropathies and neurodegenerative diseases. Competing Interest Statement The authors have declared no competing interest. Footnotes Added conditional Sarm1 knockout in Schwann Cells Electron Microscopy data supporting the argument that Schwann Cell Sarm1 contributes to the kinetics of axon degeneration Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted March 23, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Pavelec , C Cho , T. Vegiraju , J. Guo , C. Kim-Aun , S. Kucenas , N. Leitinger , J. Coutinho-Budd , J. Campbell , C. 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