4.6 Article

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke

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NEUROSCIENCE BULLETIN
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SPRINGER
DOI: 10.1007/s12264-023-01109-7

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Ischemic stroke; Monocyte-derived macrophage; Microglia; Neurogenesis; Single-cell sequencing

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Using single-cell RNA sequencing, this study investigated the composition and transcriptional features of immune cells in the peri-infarct region after cerebral ischemia. Microglia were found to be the predominant cell type with diverse activation patterns. Infiltrated monocyte-derived macrophages exhibited a gradual transition to activation. Interactions between macrophages and microglia promoted anti-inflammatory and repair-promoting microglia phenotypes and post-stroke neurogenesis.
Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

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