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Publication : Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice.

First Author  O'Shea TM Year  2024
Journal  Nat Neurosci Volume  27
Issue  8 Pages  1505-1521
PubMed ID  38907165 Mgi Jnum  J:363153
Mgi Id  MGI:8159126 Doi  10.1038/s41593-024-01684-6
Citation  O'Shea TM, et al. (2024) Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice. Nat Neurosci 27(8):1505-1521
abstractText  Central nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes; however, fundamental features of these cells are poorly understood. Here we show that following spinal cord injury or stroke, 90% and 10% of border-forming astrocytes derive, respectively, from proliferating local astrocytes and oligodendrocyte progenitor cells in adult mice of both sexes. Temporal transcriptome analysis, single-nucleus RNA sequencing and immunohistochemistry show that after focal CNS injury, local mature astrocytes dedifferentiate, proliferate and become transcriptionally reprogrammed to permanently altered new states, with persisting downregulation of molecules associated with astrocyte-neuron interactions and upregulation of molecules associated with wound healing, microbial defense and interactions with stromal and immune cells. These wound repair astrocytes share morphologic and transcriptional features with perimeningeal limitans astrocytes and are the predominant source of neuroprotective borders that re-establish CNS integrity around lesions by separating neural parenchyma from stromal and immune cells as occurs throughout the healthy CNS.
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