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Regionally diverse astrocyte subtypes and their heterogeneous response to EAE
Author(s) -
Borggrewe Malte,
Grit Corien,
Vainchtein Ilia D.,
Brouwer Nieske,
Wesseling Evelyn M.,
Laman Jon D.,
Eggen Bart J. L.,
Kooistra Susanne M.,
Boddeke Erik W. G. M.
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23954
Subject(s) - astrocyte , biology , central nervous system , neuroinflammation , neuroscience , forebrain , hindbrain , transcriptome , experimental autoimmune encephalomyelitis , microglia , aquaporin 4 , immunology , neuroglia , gene expression , inflammation , gene , genetics , biochemistry
Astrocytes fulfil many functions in the central nervous system (CNS), including contribution to the blood brain barrier, synapse formation, and trophic support. In addition, they can mount an inflammatory response and are heterogeneous in morphology and function. To extensively characterize astrocyte subtypes, we FACS‐isolated and gene expression profiled distinct astrocyte subtypes from three central nervous system regions; forebrain, hindbrain and spinal cord. Astrocyte subpopulations were separated based on GLAST/SLC1A3 and ACSA‐2/ATP1B2 cell surface expression. The local brain environment proved key in establishing different transcriptional programs in astrocyte subtypes. Transcriptional differences between subtypes were also apparent in experimental autoimmune encephalomyelitis (EAE) mice, where these astrocyte subtypes showed distinct responses. While gene expression signatures associated with blood–brain barrier maintenance were lost, signatures involved in neuroinflammation and neurotoxicity were increased in spinal cord astrocytes, especially during acute disease stages. In chronic stages of EAE, this reactive astrocyte signature was slightly decreased, while obtaining a more proliferative profile, which might be relevant for glia scar formation and tissue regeneration. Morphological heterogeneity of astrocytes previously indicated the presence of astrocyte subtypes, and here we show diversity based on transcriptome variation associated with brain regions and differential responsiveness to a neuroinflammatory insult (EAE).