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Integrated meta-analysis of human astrocytes transcriptomes reveals a candidate recurrent inflammatory signature in response to inflammatory and immune stimuli
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DOI：10.3389/fncel.2026.1870142.png)
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Abstract
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Astrocytes are key regulators of inflammatory and immune responses in the central nervous system; particularly under pathological conditions. We conducted a systematic search of the NCBI GEO and ENA databases to identify transcriptomic studies of stimulated astrocytes. This meta-analysis integrates 11 RNA-Seq datasets; encompassing a total of 153 samples (91 stimulated; and 62 controls) exposed to pro-inflammatory stimuli such as cytokines (TNF-α; IL-6; and IL-1β); palmitic acid; and pathogens like SARS-CoV-2 and Borrelia burgdorferi. Through robust rank aggregation (RRA); we identified 130 differentially expressed genes (DEGs); including 125 upregulated and 5 downregulated. Functional enrichment analyses revealed that these DEGs are primarily involved in immune and inflammatory pathways; such as cytokine signaling; interferon responses; and NF-κB activation. Network analysis revealed five hub nodes; CXCL10; DDX58; IFIH1; IL-1β; and TLR3; underscoring their importance in astrocytic inflammatory signaling. These findings emphasize the ability of astrocytes to act as immunocompetent cells that coordinate inflammatory responses through mechanisms such as the NOD-like receptor and NF-κB pathways. Although chronic activation of NF-κB has been linked to inflammation; this pathway also plays essential roles in synaptic plasticity. Moreover; the consistent upregulation of DDX58 and IFIH1 across varied inflammatory stimuli suggests that astrocytes transition into a common ‘reactive’ state that may contribute to chronic neuroinflammation. This study identifies a candidate gene signature and underscores the dual protective and pathological roles of astrocytes in inflammatory processes.
Keywords:
astrocytes
meta-analysis
neuroinflammation
RNA-seq
transcriptome profiling
robust rank aggregation
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