Transcription Factor BCL11A Regulates Schwann Cell Behavior During Peripheral Nerve Regeneration

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.