Single-cell RNA-seq uncovers novel metabolic functions of Schwann cells beyond myelination.
J Neurochem
; 166(2): 367-388, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-37328915
ABSTRACT
Schwann 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 stress. Mapping SC intercellular communication identified a shift in communication, centered on immune response and trophic support pathways, which primarily impacted nonmyelinating SCs. Validation analyses revealed that neuropathic SCs become pro-inflammatory and insulin resistant under prediabetic conditions. Overall, our study offers a unique resource for interrogating SC function, communication, and signaling in nerve pathophysiology to help inform SC-specific therapies.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estado Prediabético
/
Enfermedades del Sistema Nervioso Periférico
Límite:
Animals
/
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article