Single − Cell Transcriptomic Landscape of Sciatic Nerve After Transection Injury

Peripheral nerve injuries, especially those involving the sciatic nerve, often result in persistent deficits with limited treatment options. To dissect the cellular mechanisms of nerve repair, we performed single − cell RNA sequencing on rat sciatic nerves at seven time points (Day 0, 1, 3, 5, 7, 10, 14) following transection injury. We identified dynamic changes in four major cell compartments—neurofibroblasts (NFs), glial cells (Glis), immune cells, and vascular cells. Early responses (Day 1) featured immune cell infiltration, followed by expansion of proliferative mesenchymal cells (NF5) and repair Schwann cells (Gli0) by Day 3–5. Vascular cells expanded from Day 7 to Day 10, and by Day 14, Glis transitioned into mature myelinating states while NF and immune cells stabilized. Compared to crush injury, transection induced a stronger early immune response and delayed Schwann cell recovery. These findings provide a time − resolved atlas of sciatic nerve regeneration and highlight stage − specific therapeutic targets, particularly macrophage activation and NF–Gli signaling.