Project description:We investigated the effect of Lecanemab's Fc effector function on the transcriptomes of human microglia xenotransplanted in a mouse model of AD. We performed Nova-ST spatial transcriptomics analysis on xenografted mice treated with Lecanemab and Lecanemab LALA-PG, a human IgG1 variant designed to abolish Fc-mediated effector functions. We found that treatment with Lecanemab induced phagocytic and lysosomal reprogramming in the microglia surrounding plaques, an effect that was not present upon Lecanemab LALA-PG.
Project description:We used primary mouse microglia to determine whether Bruton's tyrosine kinase (BTK) inhibition could attenuate differential gene expression induced by Fc receptor stimulation.
Project description:Esophageal cancer-related gene 4 (Ecrg4), a hormone-like peptide, is thought to be a tumor suppressor, however little is known about the mechanism of how Ecrg4 suppresses tumorigenesis. Using the mouse glioma–initiating cell models, we identified Ecrg4 acts as a tumor suppressor in vivo. To characterize the function of Ecrg4 towards microglia, an innate immune cell in central nervous system, we performed gene expression microarray analysis for primary microglia treated with or without recombinant Fc-fused Ecrg4 fragments. We demonstrate here that Ecrg4 fragments, amino acid residues 71-132 and 133-148, which are produced by the proteolitic cleavage, induced the expression of pro-inflammatory cytokines in microglia. Thus, Ecrg4 acts as a cytokine/chemokine inducer, which activates the immune cells to eradicate tumor.
Project description:To identify the genes involved in the anti-influenza activity of Mel56, we performed an RNA sequencing (RNA-seq) analysis of IAV-infected MDCK cells treated with Mel56. A total of 1,767 differentially expressed genes (DEGs) were identified using |fold-change (FC)| ≥ 2 and raw p-value < 0.05 as thresholds for the comparison between Mel56-treated and DMSO-treated MDCK cells infected with A/PR/8/34 virus. Among these DEGs, 1,062 were upregulated and 705 were downregulated (≥2-FC) in response to Mel56 treatment.
Project description:We used human induced pluripotent stem cell (iPSC)-derived microglia to determine whether Bruton's tyrosine kinase (BTK) inhibition could attenuate differential gene expression induced by Fc receptor stimulation.
Project description:Expression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation.
Project description:We used a human induced pluripotent stem cell (iPSC)-derived tri-cultures, comprised of neurons, astrocytes, and microglia, to determine whether Bruton's tyrosine kinase (BTK) inhibition could attenuate differential gene expression induced by Fc receptor stimulation.
Project description:Nervous system inflammation and microglia activation are among hallmarks of Parkinson’s disease. Partial nigrostriatal neurodegeneration can be compensated. Interaction between neurons, microglia and astrocytes could be essential for this functional adaptation and neuronal survival in long-term, but which mechanisms are responsible is unknown. The aim was to check how astrocyte vs neuron degeneration affected differentially microglia activation proteome and which mechanisms were regulated. In a rat model of 7-day infusion by osmotic minipumps of fluorocitrate (FC) into the substantia nigra (SN) (doi: 10.1007/s12035-017-0529-z; doi: 10.1111/jnc.14605; doi: 10.1016/j.mito.2018.12.002) astrocytes become dysfunctional and die, strongly activating microglia in the process. 6-OHDA injected into medial forebrain bundle caused selective degeneration of dopaminergic neurons in the SN and only slightly activated microglia, probably via different mechanism. Controls were sham operated. Microglia cells were sorted out from dissociated SN tissue using FACS, and processed for mass spectrometry proteome analysis. Microglial response to dying astrocytes vs dying neurons was different. Understanding the role of individual cell type in the diseased tissue cellular context is essential to understand disease pathomechanisms and identify better pharmacological targets.
