Spatially resolved transcriptomics identifies intercellular signaling post-ischemic stroke that controls neural stem cell proliferation.

Ischemic stroke mobilizes adult neural stem cells (NSCs), which could be leveraged for recovery. However, the intercellular signals that activate NSCs are poorly understood. Cells located in the cerebral lesion may send signals to the NSC niche to initiate the regenerative responses. Here, we computationally inferred cell-cell communication between the ischemic infarct region and ventricular-subventricular zone (V-SVZ) NSC niche from spatial gene expression profiles and identified ligand-receptor pairs in the signal transduction events at three time points. Further, we detailed the regulatory function of galectin-9 on the proliferation of NSCs as a checkpoint molecule that guards the responses of NSCs under physiological conditions. In addition, we show that TIM-3 may mediate the inhibitory effect of galectin-9 on NSC proliferation. Collectively, these data reveal galectin-9 as an important regulator of NSC proliferation under both physiological and injury conditions.