A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2
Spinal cord injury (SCI) triggers a cascade of intricate molecular and cellular changes that determine the outcome. In this study, we resolve the spatiotemporal organization of the injured mouse spinal cord and quantitatively assess in situ cell-cell communication following SCI. By analyzing existing single-cell RNA-sequencing datasets alongside our spatial data, we delineate a subpopulation of Igfbp2-expressing astrocytes that migrate from the white matter (WM) to grey matter (GM) and become reactive upon SCI, termed as Astro-GMii. Further, Igfbp2 upregulation promotes astrocyte migration, proliferation and reactivity, and the secreted IGFBP2 protein fosters neurite outgrowth. Finally, we show that IGFBP2 significantly reduces neuronal loss and remarkably improves the functional recovery in a mouse model of SCI in vivo. Together, this study not only provides a comprehensive molecular atlas of SCI but also exemplifies how the rich resource can be applied to endow cells and genes with functional insight and therapeutic potential. Overall design: 64 spinal cord sections from 9 different C57BL/6J mice were sequenced using 10x Visium, including different position and timepoints. There were 4 distances of rostral (-) and the caudal (+) sections at ±0.5 and ±1.0 mm from the transection injury epicenter and four time points 0 (uninjured), 3, 24 and 72 hpi. Four consecutive cryosections of the same distance at each time points were attached to the same Visium Gene Expression slide.