iSNAT

iSNAT maps dynamic cellular and molecular responses in the murine sciatic nerve after peripheral nerve injury using single-cell RNA sequencing to characterize degeneration and regeneration.

Key Features:

• Single-Cell Analysis: High-resolution single-cell RNA sequencing of naïve and injured mouse sciatic nerve populations, including peripheral blood mononuclear cells, monocytes, macrophages, endoneurial and perineurial stromal cells.
• Temporal Dynamics: Profiles cellular composition at 1 day, 3 days, and 7 days post-injury to capture temporal progression of immune infiltration and metabolic changes.
• Metabolic Reprogramming: Identifies a shift from glycolytic proinflammatory monocytes/macrophages to inflammation-resolving macrophages favoring oxidative phosphorylation during early repair.
• Immune Microenvironments: Defines distinct, location-specific immune compartments triggered by mechanical wounding and Wallerian degeneration.
• Intercellular Communication Networks: Uses CellChat to analyze hundreds of ligand–receptor interactions and map cell–cell communication in naïve and injured states.
• Blood-Nerve Barrier Dynamics: Documents partial blood–nerve barrier leakiness after injury that permits entry of serum proteins and immune cells into nerve tissue.
• Validation with Sarm1-/- Mice: Corroborates observations using Sarm1-/- mice in which Wallerian degeneration is delayed.

Scientific Applications:

• Mechanistic studies: Enables investigation of molecular and cellular processes governing neural tissue degeneration and regeneration.
• Therapeutic target discovery: Facilitates identification of targets by elucidating immune cell interactions and metabolic pathways involved in nerve repair.
• Comparative injury modeling: Supports comparative analyses across injury models to dissect intrinsic and extrinsic determinants of peripheral nervous system recovery.

Methodology:

Single-cell RNA sequencing data were analyzed with CellChat for ligand–receptor interaction mapping and with additional bioinformatics analyses to map cellular interactions and metabolic changes over time.