A Single-cell Spatiotemporal Atlas Encoding Age-dependent Evolution of the Ischemic Penumbra
Aging is the predominant risk factor for stroke and a major driver of poor neurological recovery. Although the ischemic penumbra represents a key therapeutic target, its age-dependent molecular landscape remains poorly understood. Here, we generated a spatiotemporal transcriptomic atlas of the post-stroke penumbra in young (3-4 months) and aged (19-20 months) mice at acute (day 3) and chronic…
The prevalence of stroke escalates with age, exacerbating detrimental neurological outcomes. The ischemic penumbra, a critical therapeutic target, exhibits an incompletely understood age-dependent molecular profile. Researchers generated a spatiotemporal transcriptomic atlas of the post-stroke penumbra in both young (3-4 month-old) and aged (19-20 month-old) mice at two time points following transient focal cerebral ischemia: acute (day 3) and chronic (day 14).
By combining spatial transcriptomics with single-cell RNA sequencing, the researchers identified a persistent transcriptomic penumbra (TP) observable for up to 14 days post-stroke, surpassing the timeframe typically inferred by traditional imaging techniques.
The aging process significantly influenced the TP organization, leading to dysregulated energy metabolism, impaired neurovascular repair, diminished pro-reparative cell-cell communication, and extensive remodeling of transcriptional regulatory networks. Utilizing this atlas, the team pinpointed regulatory hub genes whose functional disruption could concurrently mitigate several age-related pathological pathways.
The assembled data delineate the molecular architecture of the aging post-stroke penumbra and furnish a publicly available platform for mechanistic exploration and therapeutic target identification, with the ultimate goal of enhancing recovery following stroke.
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