Single-Cell Transcriptomic Analysis of Astrocytes 12 Hours after Ischemic Stroke.

Reactive astrocytes are detrimental or protective in ischemic stroke. However, the mechanisms of these effects are not entirely clear. We investigated the heterogeneity of mice astrocytes 12 h after cerebral ischemia-reperfusion via Single-cell RNA sequencing. We acquired astrocyte subclusters’ transcriptional characteristics involving diversified functions. We identified 9 genes as potential therapeutic targets and 6 genes were specific to astrocyte subcluster 2. Additionally, we explored the effects of melatonin and stattic on the transformation of astrocytes to the A2 phenotype. TTC stain, grip strength test and immunofluorescence were used. We revealed melatonin promoted the transformation of astrocytes to the A2 phenotype, the effect was related to STAT3 and inhibited by Stattic. Our study may lay a foundation for untangling the difference between astrocyte subclusters 12 h after stroke and elucidating the mechanisms of A2 astrocyte transformation 3 d after stroke. Single-cell transcriptome analysis of two samples:one was a mixture of ischemic brain tissue from three MCAO model mice, the other was a mixture of brain tissue in the same area as the former from three sham mice.