Project Details
Projekt
Epigenetic Priming of Astrocytes by Early-Life Neuroinflammation: The Role of the SWI/SNF/BAF Complex
Subject Area
Developmental Neurobiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 563453265
Early life neuroinflammation is considered to promote the development of a number of CNS pathologies. Our previous data indicate that pharmacological inhibition of the SWI/SNF/BAF chromatin remodeling complex abrogates the astrocytic inflammatory response. Here we aim at exploring (i) whether an early inflammatory event will prime astrocytes for an epigenetically encoded hyperreactive state that impacts astrocyte responses to subsequent inflammatory events, and (ii) the role of the SWI/SNF/BAF complex in this process. To that end, we will inactivate the SWI/SNF/BAF complex subunit BCL7A in mouse astrocytes and human brain organoids. To model the ‘double-hit’ neuroinflammatory scenario in both mice and human organoids, two consecutive injections of Lipopolysaccharide or treatments with the proinflammatory factors, TNF, IL1alpha and C1q will be used, respectively. Analysis of astrocyte reactivity, RNA sequencing and ATAC sequencing will be employed to assess the inflammatory response in native versus pre-exposed astrocytes as well as transcriptional changes and chromatin modifications that might be associated with epigenetic priming of a hyperreactive state.
DFG Programme
Priority Programmes
