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Series GSE245382 Query DataSets for GSE245382
Status Public on Dec 01, 2023
Title Astrocyte-produced HB-EGF limits autoimmune CNS pathology [WGBS]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Central nervous system (CNS) resident cells such as microglia, oligodendrocytes and astrocytes are gaining increasing attention in respect to their contribution to CNS pathologies including Multiple Sclerosis (MS). Several studies have demonstrated the involvement of pro- inflammatory glial subsets in the pathogenesis and propagation of inflammatory events in MS and its animal models. However, it has only recently become clear that the underlying heterogeneity of astrocytes and microglia can not only drive inflammation, but also lead to its resolution through direct and indirect mechanisms. Failure of these tissue-protective mechanisms may potentiate disease and increase the risk of conversion to progressive stages of MS, for which currently available therapies are limited. Using proteomic analyses of cerebrospinal fluid specimens from MS patients in combination with experimental studies, we here identify Heparin-binding EGF-like growth factor (HB-EGF) as a central mediator of tissue-protective and anti-inflammatory effects important for the recovery from acute inflammatory lesions in CNS autoimmunity. Hypoxic conditions drive the rapid upregulation of HB-EGF by astrocytes during early CNS inflammation, while pro-inflammatory conditions suppress trophic HB-EGF signaling through epigenetic modifications. Finally, we demonstrate both anti-inflammatory and tissue-protective effects of HB-EGF in a broad variety of cell types in vitro and use intranasal administration of HB-EGF in acute and post-acute stages of neuroinflammation to attenuate disease in a preclinical mouse model of MS. Altogether, we identify astrocyte-derived HB-EGF and its epigenetic regulation as a novel modulator of autoimmune CNS inflammation and potential therapeutic target in MS.
 
Overall design Whole Genome Bisulfite Sequencing (WGBS) of FACS sorted naive astrocytes and from peak experimental autoimmune encephalomyelitis (EAE)
 
Contributor(s) Linnerbauer M, Rothhammer V, Jagodic M, Kular L, Ewing E, Needhamsen M, Han Y
Citation(s) 38409259
Submission date Oct 14, 2023
Last update date Mar 01, 2024
Contact name Mathias Linnerbauer
Organization name University Hospital Erlangen
Department Neurology
Street address Schwabachanlage 6
City Erlangen
ZIP/Postal code 91054
Country Germany
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM7841629 A1
GSM7841630 A2
GSM7841631 A3
This SubSeries is part of SuperSeries:
GSE245383 Astrocyte-produced HB-EGF limits autoimmune CNS pathology
Relations
BioProject PRJNA1028108

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE245382_RAW.tar 1.6 Gb (http)(custom) TAR (of COV)
SRA Run SelectorHelp
Raw data are available in SRA

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