Disentangling glial diversity in peripheral nerves at single-nuclei resolution

The peripheral nerve contains diverse cell types that support its proper function and maintenance. In this study, we analyzed multiple peripheral nerves using single-nuclei RNA sequencing, which allowed us to circumvent difficulties encountered in analyzing cells with complex morphologies via conventional single-cell methods. The resultant mouse peripheral nerve cell atlas highlights a diversity of cell types, including multiple subtypes of Schwann cells (SCs), immune cells and stromal cells. We identified a distinct myelinating SC subtype that expresses Cldn14, Adamtsl1 and Pmp2 and preferentially ensheathes motor axons. The number of these motor-associated Pmp2⁺ SCs is reduced in both an amyotrophic lateral sclerosis (ALS) SOD1^G93A mouse model and human ALS nerve samples. Our findings reveal the diversity of SCs and other cell types in peripheral nerve and serve as a reference for future studies of nerve biology and disease.