An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury

• Type of Material: Article
• Authors: Amanda B Lutz, Stanford University; Tawaun A Lucas, Stanford University; Gleen A Carson, Stanford University; Christine Caneda, Stanford University; Lu Zhou, Stanford University; Ben A Barres, Stanford University; Marion S Buckwalter, Stanford University; Steven Sloan, Emory University
• Language: English
• Date: 2022-04-30
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12974-022-02462-6
• Title of Journal or Parent Work: JOURNAL OF NEUROINFLAMMATION
• Volume: 19
• Issue: 1
• Start Page: 105
• End Page: 105
• Grant/Funding Information: This work was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (B.A.B.), Christopher and Dana Reeve Foundation (B.A.B.), NIH Grants EY11310, NS069375, 1S10RR02678001, and NIH S10 Shared Instrument Grant S10RR027431-01 (to B.A.B.), NIH Grant T32 HD007249 Developmental and Neonatal Biology Training Program (to A.B.L.), National Institute of Mental Health Grants T32GM007365, F30MH106261, R01MH125956 (to S.A.S) Bio-X Fellowship (to S.A.S.), the NARSAD Brain and Behavior Young Investigator Award (to S.A.S.) and the Stanford Medical Scientist Training Program and School of Medicine (A.B.L.). M.S.B received funding from an AHA/Allen Brain Health Award (19PABHI34580007) and Foundation Leducq (19CVD01).
• Keywords: AXON; Transcriptome; Regeneration; PROLIFERATION; MYELIN; REGENERATION; Peripheral nerve; Schwann cell; Life Sciences & Biomedicine; Neurosciences; Neuroinflammation; GROWTH; Injury response; PROTEINS; Immunology; Macrophage; Science & Technology; Neurosciences & Neurology; PATHWAY; Repair cell; LINEAGE
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Obstetrics and Gynecology

Abstract

Background: The important contribution of glia to mechanisms of injury and repair of the nervous system is increasingly recognized. In stark contrast to the central nervous system (CNS), the peripheral nervous system (PNS) has a remarkable capacity for regeneration after injury. Schwann cells are recognized as key contributors to PNS regeneration, but the molecular underpinnings of the Schwann cell response to injury and how they interact with the inflammatory response remain incompletely understood. Methods: We completed bulk RNA-sequencing of Schwann cells purified acutely using immunopanning from the naïve and injured rodent sciatic nerve at 3, 5, and 7 days post-injury. We used qRT-PCR and in situ hybridization to assess cell purity and probe dataset integrity. Finally, we used bioinformatic analysis to probe Schwann cell-specific injury-induced modulation of cellular pathways. Results: Our data confirm Schwann cell purity and validate RNAseq dataset integrity. Bioinformatic analysis identifies discrete modules of genes that follow distinct patterns of regulation in the 1st days after injury and their corresponding molecular pathways. These findings enable improved differentiation of myeloid and glial components of neuroinflammation after peripheral nerve injury and highlight novel molecular aspects of the Schwann cell injury response such as acute downregulation of the AGE/RAGE pathway and of secreted molecules Sparcl1 and Sema5a. Conclusions: We provide a helpful resource for further deciphering the Schwann cell injury response and a depth of transcriptional data that can complement the findings of recent single cell sequencing approaches. As more data become available on the response of CNS glia to injury, we anticipate that this dataset will provide a valuable platform for understanding key differences in the PNS and CNS glial responses to injury and for designing approaches to ameliorate CNS regeneration.