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Effect of mRNA vaccine on Epigenetic and Transcriptomic Profiles of Kupffer Cells (RNA-Seq)

ABSTRACT: The result show that an mRNA/LNP vaccine induced significant numbers of differentially expressed genes (DEG). The analysis identified 123 DEGs between control PBS and mRNA/LNP vaccinated groups where 23 genes and 100 genes were upregulated and downregulated, respectively, in the mRNA/LNP group. To understand the biological changes from the transcriptomic data, gene set enrichment analysis (GSEA) was performed using the whole transcriptome data set. GSEA identified the biological pathways associated with interferon gamma response and protein secretion as the top two ‘Hallmark’ gene sets enriched in OVA mRNA/LNP group, compared to PBS group.

ORGANISM(S): Mus musculus

PROVIDER: GSE267045 | GEO | 2024/11/06

REPOSITORIES: GEO

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Project description:The perinatal period and early infancy are considered critical periods for lung development, and adversities during this period are believed to impact lung health in adulthood.The main factors affecting postnatal lung development and growth include environmental exposures, cigarette smoking, (viral) infections, allergic sensitization, and asthma.Therefore, we hypothesized that concomitant exposure in the early postnatal period in mice would cause more profound alterations in lung alveolarization and growth in adult life, quantified by stereology, and differently modulate lung inflammation and gene expression than either insult alone.Five-day-old male mice were immunized intraperitoneally (i.p.) with 10 µg of ovalbumin (OVA). This procedure was repeated at the 7th day of life, animals from the control group received i.p. injection of PBS only. Mice were exposed to either ambient PM2.5 or filtered air from the 5th to the 39th day of life, using an ambient particle concentrator developed at the Harvard School of Public Health (HAPC).Total RNA of lung samples (n=3 animals per group) was extracted using RNeasy Mini Kit (Qiagen, Hilden, Germany), according to manufacturer's instructions. The microarray analysis was performed using three RNA samples for each studied group (Control, OVA, PM2.5, OVA+PM2.5), totalizing 12 samples. One hundred nanograms of total RNA was ampliﬁed with the Ambion WT Expression Kit and hybridized onto the GeneChip Mouse Gene 2.0 ST Array (Thermo Scientific, Massachusetts, USA), following manufacturer’s protocol. The comparison between the control and OVA group exhibit 32 DEGs (28 up-regulated and 4 down-regulated), between the control and PM2.5 group had 6 DEGs (4 up and 2 down) and between the control and OVA+PM2.5 group had 5 DEGs (4 up and 1 down). The comparison between OVA and PM2.5 group showed 97 DEGS (22 up and 75 down) and between OVA and OVA+PM2.5 group had 7 DEGs (4 up and 3 down). Finally, the comparison between the PM2.5 and OVA+PM2.5 group exhibit 34 DEGs (2 up and 32 down).Our experimental data provide pathological support for the hypothesis that either allergic or environmental insults in early life have permanent adverse consequences to lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice.

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Effect of mRNA vaccine on Epigenetic and Transcriptomic Profiles of Kupffer Cells (RNA-Seq)

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