The code of this analysis can be found in gpenglab's github
Wang et al. conducted a comprehensive spatial transcriptomic analysis that provides a rich resource and a useful bioinformatic toolkit for disentangling the spatiotemporal re-organization of the injured spinal cord. They further spatially identified a subpopulation of injuryinduced migrating astrocytes that secrete IGFBP2, which exhibits potent neuroprotection following SCI.
A comprehensive and dynamic molecular atlas of the spinal cord after acute injury
In situ depiction of cell-cell communication following spinal cord injury (SCI)
Spatial delineation of SCI-induced, WM-to-GM migrating Igfbp2+-astrocytes
IGFBP2 treatment improves neuronal survival and functional outcomes of SCI in vivo
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.
Cite: doi: 10.1016/j.devcel.2024.06.016
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Regulon activity during early spinal cord injury
Regulon's target genes:
Exploring the ligand-receptor interaction between potential cell type pair