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Molecular and Regenerative Characterization of Repair and Non-repair Schwann Cells

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Abstract

Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs. The RSCs upregulate a group of genes that are related to inflammation, repair, and regeneration, whereas non-RSCs upregulate genes related to myelin maintenance, Notch, and aging. These findings indicate that the RSCs have markedly different cellular, regenerative, and molecular characteristics compared to the non-RSCs, even though the RSCs were just derived from non-RSCs upon injury, thus providing the basis for understanding the mechanisms related to SC mediated repair after peripheral nerve injury.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Sequence data that support the findings of this study were deposited in Gene Expression Omnibus under the accession code GSE188399.

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Acknowledgements

This study was supported by the General Insurance Association of Japan, a Grant-in-Aid for Scientific Research (JP20K18016, JP20H03558), and the Japan Agency for Medical Research and Development (JP21gm6210004), the Kobayashi Foundation, and the SEI Group CSR Foundation. We wish to express our appreciation for M. Endo for her assistance, the National BioResource Project-Rat (http://www.anim.med.kyoto-u.ac.jp/NBR/) for providing LEW-Tg (Gt(ROSA)26Sor-DsRed*)7Jmck rat (#0404), and the Open Facility, Hokkaido University Sousei Hall for providing access to the cryostat.

Funding

This study was supported by the General Insurance Association of Japan, a Grant-in-Aid for Scientific Research (JP20K18016, JP20H03558), and the Japan Agency for Medical Research and Development (JP21gm6210004), the Kobayashi Foundation, and the SEI Group CSR Foundation.

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Contributions

Conceptualization: TS and KK, Methodology: TE and KK, Investigation: TS and TE, Funding acquisition: KK, Project administration: KK, Supervision: NI, Writing: TS and KK.

Corresponding author

Correspondence to Ken Kadoya.

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The authors declare no competing interests.

Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki and carried out in accordance with the recommendations of the local ethical committee of Hokkaido University (15-0097). The protocol was approved by the local ethical committee of Hokkaido University.

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Suzuki, T., Kadoya, K., Endo, T. et al. Molecular and Regenerative Characterization of Repair and Non-repair Schwann Cells. Cell Mol Neurobiol 43, 2165–2178 (2023). https://doi.org/10.1007/s10571-022-01295-4

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  • DOI: https://doi.org/10.1007/s10571-022-01295-4

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