Astrocyte-Specific Deletion of Sox2 Promotes Functional Recovery After Traumatic Brain Injury

Chunhai Chen, Xiaoling Zhong, Derek K. Smith, Wenjiao Tai, Jianjing Yang, Yuhua Zou, Lei Lei Wang, Jiahong Sun, Song Qin, Chun-Li Zhang

Research output: Contribution to journalArticle

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Abstract

Injury to the adult brain induces activation of local astrocytes, which serves as a compensatory response that modulates tissue damage and recovery. However, the mechanism governing astrocyte activation during brain injury remains largely unknown. Here we provide in vivo evidence that SOX2, a transcription factor critical for stem cells and brain development, is also required for injury-induced activation of adult cortical astrocytes. Genome-wide chromatin immunoprecipitation-seq analysis of mouse cortical tissues reveals that SOX2 binds to regulatory regions of genes associated with signaling pathways that control glial cell activation, such as Nr2e1, Mmd2, Wnt7a, and Akt2. Astrocyte-specific deletion of Sox2 in adult mice greatly diminishes glial response to controlled cortical impact injury and, most unexpectedly, dampens injury-induced cortical loss and benefits behavioral recovery of mice after injury. Together, these results uncover an essential role of SOX2 in somatic cells under pathological conditions and indicate that SOX2-dependent astrocyte activation could be targeted for functional recovery after traumatic brain injury.

Original languageEnglish (US)
Pages (from-to)54-69
Number of pages16
JournalCerebral cortex (New York, N.Y. : 1991)
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2019

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Astrocytes
Wounds and Injuries
Neuroglia
SOXB1 Transcription Factors
Chromatin Immunoprecipitation
Nucleic Acid Regulatory Sequences
Brain
Regulator Genes
Brain Injuries
Stem Cells
Traumatic Brain Injury
Genome

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Astrocyte-Specific Deletion of Sox2 Promotes Functional Recovery After Traumatic Brain Injury. / Chen, Chunhai; Zhong, Xiaoling; Smith, Derek K.; Tai, Wenjiao; Yang, Jianjing; Zou, Yuhua; Wang, Lei Lei; Sun, Jiahong; Qin, Song; Zhang, Chun-Li.

In: Cerebral cortex (New York, N.Y. : 1991), Vol. 29, No. 1, 01.01.2019, p. 54-69.

Research output: Contribution to journalArticle

Chen, Chunhai ; Zhong, Xiaoling ; Smith, Derek K. ; Tai, Wenjiao ; Yang, Jianjing ; Zou, Yuhua ; Wang, Lei Lei ; Sun, Jiahong ; Qin, Song ; Zhang, Chun-Li. / Astrocyte-Specific Deletion of Sox2 Promotes Functional Recovery After Traumatic Brain Injury. In: Cerebral cortex (New York, N.Y. : 1991). 2019 ; Vol. 29, No. 1. pp. 54-69.
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