Single ‐cell RNA‐seq uncovers novel metabolic functions of Schwann cells beyond myelination

Using single-cell RNA sequencing, we examined the transcriptional profiles and intercellular communication of Schwann cells in the high-fat diet-fed mouse, a model of prediabetic neuropathy. We show that myelinating Schwann cells acquire a unique transcriptional profile secondary to prediabetes. We also demonstrate a shift in cellular communication, which impacts nonmyelinating Schwann cell integrity, function, and the inflammatory response. Validation analyses shows that neuropathic Schwann cells become pro-inflammatory and insulin resistant under prediabetic conditions. Overall, our study constitutes a valuable resource to advance our understanding of the cellular mechanisms underlying peripheral neuropathy and uncover Schwann cell-specific molecular targets for neuropathy treatment. AbstractSchwann cells (SCs) support peripheral nerves under homeostatic conditions, independent of myelination, and contribute to damage in prediabetic peripheral neuropathy (PN). Here, we used single-cell RNA sequencing to characterize the transcriptional profiles and intercellular communication of SCs in the nerve microenvironment using the high-fat diet-fed mouse, which mimics human prediabetes and neuropathy. We identified four major SC clusters, myelinating, nonmyelinating, immature, and repair in healthy and neuropathic nerves, in addition to a distinct cluster of nerve macrophages. Myelinating SCs acquired a unique transcriptional profile, beyond myelination, in response to metabolic str...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research