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Nascent transcription upon interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines

ABSTRACT: Changes in gene transcription regulation are necessary for species to respond to changes in their environment. In particular, host-pathogen dynamics have been observed to entail rapid evolution of genes involved in the host innate immune system. Cytokines such as type I interferon alpha and beta trigger an antiviral cellular state controlled by members of the transcription factor families STAT and IRF. However, it remains poorly understood how gene transcription regulation has been rewired through evolutionary time to achieve species-specific interferon-controlled changes in gene expression. We generated nascent transcription (PRO-seq) datasets to determine the initial transcriptional response on lymphoblastoid cell lines derived from homo sapiens and macaca mulatta upon stimulation with interferon alpha2 to assess species-specific changes in gene regulation.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE214304 | GEO | 2022/10/02

REPOSITORIES: GEO

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Project description:In the past century, recently emerged infectious diseases have become major drivers of species decline and extinction. Amphibian declines have occurred due to the fungal disease chytridiomycosis, which has exacerbated the conservation crisis of this taxonomic group. Biologists are beginning to understand what traits are important for susceptibility to this disease, but more work is needed to determine why some species succumb to disease while others do not. We conducted a laboratory experiment to examine how two toad species respond to infection in controlled environment. We selected two related species thought to differ in susceptibility â?? Bufo marinus (an invasive and putatively resistant species) and B. boreas (an endangered and putatively susceptible species). We measured infection intensity, body weight, histological changes at the site of infection, and genome-wide gene expression changes using a custom assay developed from transcriptome sequencing. Our results confirmed that the two species differ in susceptibility. The more susceptible species, B. boreas, experienced higher infection intensities, loss in body weight, more dramatic histological changes, and larger perturbations in gene expression. We found key differences in skin expression responses in multiple pathways including up-regulation of skin integrity-related genes in the resistant B. marinus. Together our results show intrinsic differences in host response between related species, which are likely to be an important factor in explaining variation in response to a deadly emerging pathogen in wild populations. We processed 72 tissue samples in total: six biological replicates, three tissue types (ventral skin, liver, spleen), two treatment groups (pathogen exposed, control), and two host species (Bufo marinus, Bufo boreas). The custom Nimblegen microarray design included 135,200 60-bp probes (excluding control probes) targeting 31,367 transcript contigs from Bufo marinus, Bufo boreas, and model species Xenopus tropicalis, with 4 probes per probe-set. We used the 12-plex microarray platform (12 arrays per glass slide). Differential expression analyses were performed separately for each tissue type and host species.

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Nascent transcription upon interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines

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