Disentangling glial diversity in peripheral nerves at single-nuclei resolution [bulk and RiboTag RNA-seq]

The peripheral nerve contains diverse cell types that support its proper function and maintenance. We analyzed multiple peripheral nerves using single-nuclei RNA-sequencing (snRNA-seq), 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 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 ALS SOD1G93A 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. Overall design: Comparison between Mpz-RiboTag enriched RNA-seq and bulk RNA-seq data for both sciatic and vagus nerves