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 gray matter (GM) and become reactive upon SCI, termed 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 this rich resource can be applied to endow cells and genes with functional insight and therapeutic potential.

中文翻译：

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小鼠脊髓损伤的时空分子图谱确定了 IGFBP2 的不同星形胶质细胞亚群和治疗潜力


脊髓损伤 （SCI） 会引发一连串复杂的分子和细胞变化，这些变化决定了结果。在这项研究中，我们解决了受伤小鼠脊髓的时空组织，并定量评估了 SCI 后的原位细胞间通讯。通过分析现有的单细胞 RNA 测序数据集和我们的空间数据，我们描绘了一个表达 Igfbp2 的星形胶质细胞亚群，这些星形胶质细胞从白质 （WM） 迁移到灰质 （GM） 并在 SCI 后产生反应，称为 Astro-GMii。此外，Igfbp2 上调促进星形胶质细胞迁移、增殖和反应性，分泌的 IGFBP2 蛋白促进神经突生长。最后，我们表明 IGFBP2 显着减少神经元丢失并显着改善体内 SCI 小鼠模型的功能恢复。总之，这项研究不仅提供了 SCI 的全面分子图谱，还举例说明了如何应用这一丰富的资源赋予细胞和基因功能洞察力和治疗潜力。