Modulation of Schwann Cell Identity by Mimicking Intercellular Communication Signals

• Applicant: Dr. Natalie Winter
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578809383

Peripheral nerve injuries often result in unsatisfactory functional recovery despite advances in microsurgical repair techniques. One major limitation is the restricted availability of suitable autologous nerve grafts, compounded by the problem of identity mismatch: Schwann cells within commonly used sensory donor grafts, such as the sural nerve, do not meet the specific requirements of regenerating motor axons. Recent research has demonstrated that Schwann cells acquire a persistent “motor” or “sensory” identity that continues even after denervation and critically determines regenerative success. The proposed project will, for the first time, systematically investigate whether this identity can be actively modulated. Its goal is to steer Schwann cell identity by mimicking physiological intercellular communication through defined ligand–receptor interactions, thereby laying the foundation for the personalized optimization of nerve grafts. The project comprises several key steps. First, Schwann cells will be differentiated from human induced pluripotent stem cells and characterized using gene expression analysis, morphology, and surface marker profiling. These naïve cells will then be exposed to carefully designed ligand cocktails based on recently identified neuron–Schwann cell signaling pathways in order to induce either motor or sensory identity. In a subsequent step, Schwann cells with a sensory identity will be targeted with motor-specific ligand combinations to shift their phenotype toward a motor identity. The effectiveness of this modulation will be validated by RNA sequencing, immunocytochemistry, and flow cytometry, while minimal ligand cocktails will be developed to achieve stable and reproducible identity changes with the smallest number of factors. In the long term, this research aims to enable intraoperative modulation of autologous or allogeneic nerve grafts, thereby improving functional recovery after peripheral nerve reconstruction and reducing donor site morbidity.

• DFG Programme: Fellowship
• International Connection: USA
• Host: Professor Ahmet Höke