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Transcription Factor BCL11A Regulates Schwann Cell Behavior During Peripheral Nerve Regeneration

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Abstract

Nerve injury-induced Schwann cell dedifferentiation helps to construct a favorable microenvironment for axon growth. Transcription factors regulate cell reprogramming and thus may be critical for Schwann cell phenotype switch during peripheral nerve regeneration. Here, we show that transcription factor B-cell lymphoma/leukemia 11A (BCL11A) is up-regulated in Schwann cells of injured peripheral nerves. Bcl11a silencing suppresses Schwann cell viability, decreases Schwann cell proliferation and migration rates, and impairs the debris clearance ability of Schwann cells. Reduced Bcl11a in injured peripheral nerves results in restricted axon elongation and myelin wrapping, leading to recovery failure. Mechanistically, we demonstrate that BCL11A may mediate Schwann cell activity through binding to the promoter of nuclear receptor subfamily 2 group F member 2 (Nr2f2) and regulating Nr2f2 expression. Collectively, we conclude that BCL11A is essential for Schwann cell activation and peripheral nerve regeneration, providing a potential therapeutic target for the treatment of peripheral nerve injury.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX21_3076] and the Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD].

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  1. Yunsong Zhang and Yinying Shen have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu, China

    Yunsong Zhang, Yinying Shen, Li Zhao, Qian Zhao, Lili Zhao & Sheng Yi

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  1. Yunsong Zhang
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  3. Li Zhao
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Contributions

Y.Z. and Y.S. designed and performed major experiments, analyzed, and interpreted experimental data. L.Z. and Q.Z. assisted with experiments and data interpretation. L.Z. and S.Y. conceived the project and wrote the manuscript.

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Correspondence to Lili Zhao or Sheng Yi.

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Animal experiments were approved ethically by the Administration Committee of Experimental Animals, Jiangsu, China, and conducted in accordance with the Institutional Animal Care Guidelines of Nantong University.

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Zhang, Y., Shen, Y., Zhao, L. et al. Transcription Factor BCL11A Regulates Schwann Cell Behavior During Peripheral Nerve Regeneration. Mol Neurobiol 60, 5352–5365 (2023). https://doi.org/10.1007/s12035-023-03432-6

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