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Distinct Cell Transcriptomic Landscapes Upon Henipavirus Infections.

ABSTRACT: Hendra virus (HeV) and Cedar virus (CedV) are henipaviruses, which fall into the Paramyxoviridae family of single-stranded, negative-sense RNA viruses. HeV is classified as a Biosafety Level-4 (BSL-4) agent, as it is highly pathogenic and is often fatal to humans. To date, no HeV prevention or treatment methods for human are available. In contrast, previous experimental infection studies have suggested that CedV is non-pathogenic. Flying foxes (pteropid bats) in Australia are the natural reservoirs of both viruses, but the cellular responses of bats to these viral infections remain unclear. Here, we infected bat and human cells with these viruses. We then examined the total transcriptomic landscapes of the cells at 6 or 24 h post infection. Unexpectedly, despite the close phylogenetic relationship between HeV and CedV, there was a dramatic difference in cellular gene expression patterns in response to the two different infections. It is likely that minor differences in the phosphoprotein (P) gene coding strategy between the two viruses cause the observed incongruence in host transcriptomic divergence and viral lethality. This study greatly expands our understanding of the pathogenic mechanisms of henipaviruses.

SUBMITTER: Chen M

PROVIDER: S-EPMC7248276 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Distinct Cell Transcriptomic Landscapes Upon Henipavirus Infections.

Chen Mingyue M Tachedjian Mary M Marsh Glenn A GA Cui Jie J Wang Lin-Fa LF

Frontiers in microbiology 20200519

Hendra virus (HeV) and Cedar virus (CedV) are henipaviruses, which fall into the <i>Paramyxoviridae</i> family of single-stranded, negative-sense RNA viruses. HeV is classified as a Biosafety Level-4 (BSL-4) agent, as it is highly pathogenic and is often fatal to humans. To date, no HeV prevention or treatment methods for human are available. In contrast, previous experimental infection studies have suggested that CedV is non-pathogenic. Flying foxes (pteropid bats) in Australia are the natural ...[more]

PMID: 32508793

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Project description:BackgroundColorectal cancer (CRC) ranks as the second-leading cause of cancer-related death worldwide with metastases being the main cause of cancer-related death. Here, we investigated the genomic and transcriptomic alterations in matching adjacent normal tissues, primary tumors, and metastatic tumors of CRC patients.MethodsWe performed whole genome sequencing (WGS), multi-region whole exome sequencing (WES), simultaneous single-cell RNA-Seq, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic colorectal cancer patients (n=84 for genomes, n=81 for exomes, n=9120 for single cells). Patient-derived tumor organoids were used to estimate the anti-tumor effects of a PPAR inhibitor, and self-renewal and differentiation ability of stem cell-like tumor cells.ResultsWe found that the PPAR signaling pathway was prevalently and aberrantly activated in CRC tumors. Blocking of PPAR pathway both suppressed the growth and promoted the apoptosis of CRC organoids in vitro, indicating that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. Using matched samples from the same patient, distinct origins of the metastasized tumors between lymph node and liver were revealed, which was further verified by both copy number variation and mitochondrial mutation profiles at single-cell resolution. By combining single-cell RNA-Seq and single-cell point mutation identification by targeted cDNA Sanger sequencing, we revealed important phenotypic differences between cancer cells with and without critical point mutations (KRAS and TP53) in the same patient in vivo at single-cell resolution.ConclusionsOur data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may serve as a rich resource for further studies.

Dataset Information

Distinct Cell Transcriptomic Landscapes Upon Henipavirus Infections.

Publications

Distinct Cell Transcriptomic Landscapes Upon Henipavirus Infections.

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