Transcriptomics,Genomics

Dataset Information

169

C/EBPβ deficiency reshapes microglial gene expression


ABSTRACT: CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage but the involvement of the various C/EBPβ expressing cell types in this neuroprotective effect is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo. In this study we have tested this hypothesis by generating mice with myeloid C/EBPβ deficiency. Mice with myeloid C/EBPβ deficiency were generated by crossing LysMCre and C/EBPβfl/fl mice . Primary microglial cultures from C/EBPβfl/fl (named here as WT) and LysMCre-C/EBPβfl/fl (named here as KO) mice were treated with lipopolysaccharide ± interferon γ (IFNγ) for 6 h and gene expression was analyzed by RNA sequencing. LysMCre-C/EBPβfl/fl mice showed an efficiency of C/EBPβ deletion of 100% in cultured microglia. Transcriptomic analysis of C/EBPβ-deficient primary microglia revealed C/EBPβ-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. This study provides new data that support a central role for C/EBPβ in the biology of activated microglia. Overall design: LysMCre-C/EBPβfl/fl genotype (12 samples): 4 samples treated with LPS, 4 with LPS +IFNg, and 4 vehicle. C/EBPβfl/fl genotype (9 samples): 3 samples treated with LPS, 3 with LPS +IFNg, and 3 vehicle. Design Case (Treatment LPS or LPS +INF) control (No treatment or vehicle) in LysMCre-C/EBPβfl/fl genotype and in C/EBPβfl/fl genotype

INSTRUMENT(S): Illumina Genome Analyzer IIx (Mus musculus)

SUBMITTER: Josep Saura  

PROVIDER: GSE90046 | GEO | 2017-06-13

SECONDARY ACCESSION(S): PRJNA354400

REPOSITORIES: GEO

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Publications

Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis.

Pulido-Salgado Marta M   Vidal-Taboada Jose M JM   Garcia Diaz-Barriga Gerardo G   Serratosa Joan J   Valente Tony T   Castillo Paola P   Matalonga Jonathan J   Straccia Marco M   Canals Josep M JM   Valledor Annabel A   Solà Carme C   Saura Josep J  

Journal of neuroinflammation 20170316 1


<h4>Background</h4>CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia  ...[more]

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