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Singel cell RNA sequencing of an F1 cross of Marek’s disease resistant and susceptible chickens

ABSTRACT: Marek's disease virus (MDV) is a highly contagious alphaherpesvirus with widespread incidence in the poultry industry. The double stranded DNA virus infects chickens and turkeys causing a lymphoproliferative disease known as Marek's disease (MD). Infected and susceptible birds develop T cell lymphomas that cause peripheral nerve degeneration, partial or complete paralysis and immunosuppression. Previously, our lab performed scRNA seq of splenic-derived cells from MD resistant Line 6 (L6) and MD susceptible Line 7 (L7) during MDV infection to identify major immune cell subsets. In this study we extend this previous analysis by adding scRNA seq of a first-generation (F1) L6 x L7 population to characterize allele specific expression in individual immune cell types. The joint analysis of scRNA seq of the L6, L7 and F1 cross provide a deeper understanding of how genetic variation impacts gene expression variation in immune cell types and identify regulatory mechanism playing a key role in MD resistance.

ORGANISM(S): Gallus gallus

PROVIDER: GSE278696 | GEO | 2025/02/04

REPOSITORIES: GEO

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Project description:Purpose: Marek's disease virus (MDV) is an oncogenic herpesvirus that can induce T-cell lymphoma. Long noncoding RNA (lncRNA) strongly associated with various cancers and many other diseases. In chickens, lncRNAs have not been comprehensively identified. Here, we profiled mRNA and lncRNA repertoires in three groups of spleens from MDV-infected and non-infected chickens, including seven tumorous spleens (TS) from MDV-infected chickens, five spleens from the survivors (SS) without any lesion after MDV infection, and five noninfected spleens (NS) from chickens, to explore the underlying mechanism of host resistance to Marek's disease (MD). Results: By using precise lncRNA identification pipeline, we identified 1315 putative lncRNAs and 1166 known lncRNAs in spleen tissue. Genomic features of putative lncRNAs were characterized. Differentially expressed mRNAs, putative lncRNAs and known lncRNAs were profiled. Some previously reported MD resistance candidate genes, such as CTLA4, HDAC9 and CD72, were also found in our differentially expressed genes list. Moreover, we found that several intergroup specifically deregulated genes were involved in important biological processes and pathways, including B cell activation and Wnt signaling pathway. We conducted co-expression network using WGCNA and identified several hub genes that may play pivotal roles in MD resistance and tumorigenesis, e.g. CTLA4, SWAP70, CXCL12 and JCHAIN. According to the expression relationship between lncRNAs and MD resistance candidate mRNAs, five deregulated lncRNAs may implicate the chicken immunity by directly or indirectly regulating those hub genes. Conclusions: We profiled both lncRNA and mRNA expression patterns in MDV-infected chicken spleens. Expression variations of intergroup specifically deregulated genes engaged in important immune process likely contributed to robust immune system in the survivors. Some oncogenesis or MD resistance related genes deregulated between groups, like CTLA4, HDAC9 and CD72 were found. Co-expression network analysis manifested that lncRNAs may affect MD resistance and tumorigenesis in chicken spleens through their impact on expression of CTLA4, SWAP70 and some other genes that are critical in many important biological processes, such as B lymphocyte proliferation and activation.

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Singel cell RNA sequencing of an F1 cross of Marek’s disease resistant and susceptible chickens

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