Synergy of epidermal growth factor (EGFR) and angiotensin II (AT1R) receptor determines composition and temporal pattern of transcriptome variation

The tyrosine kinase receptor EGFR and the G-protein-coupled receptor AT1R induce essential cellular responses, in part via receptor crosstalk with an unknown role in nuclear information transfer and transcription regulation. We investigated whether this crosstalk results in linear, EGFR-mediated nuclear signalling or in parallel, synergistic information transfer leading to qualitative and temporal variations, relevant for gene expression and environment interaction. AT1R and EGFR synergistically activate SRF via the ERK1/2-TCF and actin-MRTF pathways. Synergism, comprised of switch-like and graded single cell response, converges on the transcription factors AP1 and EGR, resulting in synergistic transcriptome alterations, in qualitative (over-additive number of genes), quantitative (over-additive expression changes of individual genes) and temporal (more late onset and prolonged expressed genes) terms. Gene ontology and IPA® pathway analysis indicate prolonged cell stress (e.g. hypoxia-like) and dysregulated vascular biology. Synergism occurs during separate but simultaneous activation of both receptors and during AT1R-induced EGFR transactivation. EGFR and AT1R synergistically regulate gene expression in qualitative, quantitative and temporal terms with (patho)physiological relevance, extending the importance of EGFR-AT1R crosstalk beyond cytoplasmic signalling.

Transcriptome atlas of Phalaenopsis equestris

The vast diversity of Orchidaceae together with sophisticated adaptations to pollinators and other unique features make this family an attractive model for evolutionary and functional studies. The sequenced genome of Phalaenopsis equestris facilitates Orchidaceae research. Here, we present an RNA-seq-based transcriptome map of P. equestris that covers 19 organs of the plant, including leaves, roots, floral organs and the shoot apical meristem. We demonstrated the high quality of the data and showed the similarity of the P. equestris transcriptome map with the gene expression atlases of other plants. The transcriptome map can be easily accessed through our database Transcriptome Variation Analysis (TraVA) for visualizing gene expression profiles. As an example of the application, we analyzed the expression of Phalaenopsis “orphan” genes–those that do not have recognizable similarity with the genes of other plants. We found that approximately half of these genes were not expressed; the ones that were expressed were predominantly expressed in reproductive structures.

Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer

The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection of factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes of HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts to reveal that HGSOC is driven by three archetypal phenotypes, defined as oncogenic states that describe the majority of the transcriptome variation. Using a multi-task learning approach to identify the biological tasks of each archetype, we identify metabolism and proliferation, cellular defense response, and DNA repair signaling as consistent cell states found across patients. Our analysis demonstrates a shift in favor of the metabolism and proliferation archetype versus cellular defense response archetype in cancer cells that received multiple lines of treatment. While archetypes are not consistently associated with specific whole-genome driver mutations, they are closely associated with subclonal populations at the single-cell level, indicating that subclones within a tumor often specialize in unique biological tasks. Our study reveals the core archetypes found in progressive HGSOC and shows consistent enrichment of subclones with the metabolism and proliferation archetype as resistance is acquired to multiple lines of therapy.

Variable dosage compensation is associated with female consequences of an X-linked, male-beneficial mutation

Recent theory has suggested that dosage compensation mediates sexual antagonism over X-linked genes. This process relies on the assumption that dosage compensation scales phenotypic effects between the sexes, which is largely untested. We evaluated this by quantifying transcriptome variation associated with a recently arisen, male-beneficial, X-linked mutation across tissues of the field cricket Teleogryllus oceanicus , and testing the relationship between the completeness of dosage compensation and female phenotypic effects at the level of gene expression. Dosage compensation in T. oceanicus was variable across tissues but usually incomplete, such that relative expression of X-linked genes was typically greater in females. Supporting the assumption that dosage compensation scales phenotypic effects between the sexes, we found tissues with incomplete dosage compensation tended to show female-skewed effects of the X-linked allele. In gonads, where expression of X-linked genes was most strongly female-biased, ovaries-limited genes were much more likely to be X-linked than were testes-limited genes, supporting the view that incomplete dosage compensation favours feminization of the X. Our results support the expectation that sex chromosome dosage compensation scales phenotypic effects of X-linked genes between sexes, substantiating a key assumption underlying the theoretical role of dosage compensation in determining the dynamics of sexual antagonism on the X.

Evolution of core archetypal phenotypes in progressive high grade serous ovarian cancer

The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To uncover phenotypic changes associated with chemotherapy resistance, we profiled single-cell RNA-sequencing (scRNA-seq) transcriptomes of HGSOC tumors collected longitudinally during patient treatment. Analysis of scRNA-seq data from two independent patient cohorts revealed that HGSOC is driven by three core archetypal phenotypes, defined as oncogenic tasks that describe the majority of the transcriptome variation. A multi-task learning approach to identify the biological tasks of each archetype identified metabolism and proliferation, cellular defense response, and DNA repair signaling. The metabolism and proliferation archetype evolved during treatment and was enriched in cancer cells from patients that received multiple-lines of treatment and had elevated tumor burden indicated by CA-125 levels. The emergence of archetypes was not consistently associated with specific whole-genome driver mutations. However, archetypes were closely associated with subclonal populations at the single-cell level, indicating that subclones within a tumor often specialize in unique biological tasks. Our study reveals the core archetypes found in progressive HGSOC and shows consistent enrichment of subclones with the metabolism archetype as resistance is acquired to multiple lines of therapy.

Transcriptome atlas of Phalaenopsis equestris

The vast diversity of Orchidaceae together with sophisticated adaptations to pollinators and other unique features make this family an attractive model for evolutionary and functional studies. The sequenced genome of Phalaenopsis equestris facilitates Orchidaceae research. Here we present an RNA-seq based transcriptome map of P. equestris which covers 19 organs of the plant including leaves, roots, floral organs and shoot apical meristem. We demonstrated the high quality of the data and showed the similarity of P. equestris transcriptome map with gene expression atlases of other plants. The transcriptome map can be easily accessed through our database Transcriptome Variation Analysis (TraVA) visualizing gene expression profiles. As an example of the application we analyzed the expression of Phalaenopsis “orphan” genes – the ones that do not have recognizable similarity with genes of other plants. We found that about a half of them are not expressed; the ones that are expressed have a predominant expression pattern in reproductive structures.

Genomic and Transcriptomic Analyses of Bioluminescence Genes in the Enope Squid Watasenia scintillans

Watasenia scintillans, a sparkling enope squid, has bioluminescence organs to illuminate its body with its own luciferase activity. To clarify the molecular mechanism underlying its scintillation, we analysed high-throughput sequencing data acquired previously and obtained draft genome sequences accomplished with comparative genomic data among the cephalopods. The genome mapped by transcriptome data showed that (1) RNA editing contributed to transcriptome variation of lineage specific genes, such as W. scintillans luciferase, and (2) two types of luciferase enzymes were characterized with reasonable 3D models docked to a luciferin molecule. We report two different types of luciferase in one organism and possibly related to variety of colour types in the W. scintillans fluorescent organs.

Mechanisms of Novel Host Use by Bactrocera tau (Tephritid: Diptera) Revealed by RNA Transcriptomes

Use of novel plant hosts can facilitate the establishment and range expansion of herbivorous invasive species. However, the inherent mechanisms of novel host use are still unclear in many herbivorous species. Here, we examine mechanisms of novel host use in the invasive tephritid fruit fly Bactrocera tau (Walker)(Diptera: Tephritidae) by documenting changes in the RNA transcriptomes associated with a novel host. RNA transcripts of B. tau were obtained with high-throughput sequencing from samples continuously reared on two traditional Cucurbitaceae hosts and a novel host (banana). We found transcriptome variation was strongly associated with feeding on banana. Moreover, B. tau feeding on banana contained more differentially expressed genes (DEGs) and more annotated categories of DEGs in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database with 1,595 DEGs and 21 major annotated pathways. The annotated categories of DEGs in individuals reared on banana differed with from those individuals feeding on other hosts and were enriched in oxidative phosphorylation, citrate cycle pathway, and four other carbohydrate pathways. For B. tau feeding on banana, the predominant numbers of upregulated genes in the mitochondrial NADH (56 on average) and a relatively higher numbers of upregulated genes (13 on average) were found in oxidative phosphorylation and the TCA pathway, respectively. Changes in RNA transcriptomes associated with novel host use, especially for genes related to energy and carbohydrate metabolism, help to explain how B. tau can be successful in use of novel hosts and may be useful in developing novel strategies for control of tephritid flies.