A velvet transcription factor specifically activates mating through a novel surface protein in the human fungal pathogen Cryptococcus deneoformans
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PROVIDER: PRJNA804126 | ENA |
REPOSITORIES: ENA
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Project description:Sexual reproduction facilitates infection by the production of both a lineage advantage and infectious sexual spores in the ubiquitous human fungal pathogen Cryptococcus deneoformans. However, the regulatory determinants specific for initiating mating remain poorly understood. Here, we identified a velvet family regulator, Cva1, that strongly promotes sexual reproduction in C. deneoformans. This regulation was determined to be specific, based on a comprehensive phenotypic analysis of cva1 under 25 distinct in vitro and in vivo growth conditions. We further revealed that Cva1 plays a critical role in the initiation of early mating events, especially sexual cell-cell fusion, but is not important for the late sexual development stages or meiosis. Thus, Cva1 specifically contributes to mating activation. Importantly, a novel mating-responsive surface protein, Cfs1, serves as the key target of Cva1 during mating, since its absence nearly blocks cell-cell fusion in C. deneoformans and its sister species C. neoformans. Together, our findings provide insight into how C. deneoformans ensures regulatory specificity of mating.
2022-02-10 | GSE196267 | GEO
Project description: Not available
| S-EPMC9241590 | biostudies-literature
Project description:We have previously described the reindeer antler velvet as a highly unique mammalian model of adult skin regeneration as wounds on backskin form a raised, contractile scar devoid of appendages or pigment, whereas identical wounds in antler velvet exhibit scar-less regeneration. To ask whether regenerative capacity is inherent to cells within the velvet (and not due to factors derived from the antler environment), we transplanted full thickness velvet skin grafts onto dorsal backskin. This scRNA-Seq sample profiles cells within the ectopic velvet graft to assess their molecular resemblance to regenerative velvet or non-regenerative dorsal backskin.
2022-12-08 | GSE153095 | GEO
Project description:Sexual reproduction facilitates infections and adaptations in Cryptococcus pathogens that cause fatal meningoencephalitis and have two distinct sexual cycles (bisexual and unisexual). Here, by constructing a gene-deletion strains library for transcription factor (TF) genes in Cryptococcus deneoformans, we explore spatiotemporal TF networks in sequential stages of mating community development and identified key regulators that determine processes specific to different reproductive modes. We show that the TFs crucial for bisex-specific syngamy coordinately induce the expression of a specific group of genes centered on the ancient mating determinants, which includes FMP1, a previously unidentified component of the conserved fungal mating pathway. Furthermore, we identify that a recently evolved regulatory cascade mediates the pre-meiotic autodiploidization process that defines Cryptococcus unisex, supporting that unisex is a recent evolutionary innovation. Our findings indicate that genetic circuits with different evolutionary ages govern the hallmark events distinguishing unisex and bisex, enabling reproductive flexibility that benefits Cryptococcus pathogenicity.
2022-11-24 | GSE135566 | GEO
Project description:An RNAseq-based transcriptomic comparison of Botrytis cinerea wild type and the three VELVET mutants was performed, to correlate common virulence defects of the mutants with changes in gene expression. A large number of genes encoding infection-related and secreted proteins was strongly underexpressed in the mutants, in particular genes encoding proteases and carbohydrate active enzymes. Many VELVET-regulated genes were found to be upregulated in the wild type during host plant infection (Müller et al.: Investigations on VELVET regulatory mutants confirm the role of host tissue acidification and secretion of proteins in pathogenesis of Botrytis cinerea; New Phytologist, 2018)
2018-04-02 | GSE112580 | GEO
Project description:The female’s reproductive tract is exposed directly to the male’s ejaculate, making it a hotspot for mating-induced responses shortly after mating. In Drosophila melanogaster, changes in the reproductive tract are essential to optimize fertilization. To detect the earliest gene regulatory events that underlie these changes, we measured transcript abundances using RNA-seq and microRNA-seq of reproductive tracts of unmated females and females collected within 10-15 minutes after the end of mating, either to a wildtype male or to a male with defective BMP signaling in secondary cells of the accessory gland, which influences the composition of the male’s ejaculate. We observed transcript abundance changes for genes with roles in tissue morphogenesis, wound healing, the immune response and metabolism. Strikingly, predicted targets of microRNAs that respond to mating are enriched for overlapping functions, suggesting that mating-induced changes are in part regulated by microRNAs. Most of the differentially expressed RNAs are upregulated in response to mating, while most of the differentially expressed microRNAs are downregulated. This pattern suggests a response of activation and de-repression of gene programs that switch the reproductive tract to a “mated” state, rather than a repression of virgin-specific programs. Male genotype did not influence transcript levels, indicating that the earliest transcriptomic responses in the reproductive tract are not dependent on ejaculate components that require BMP signaling in secondary cells. Our results shed light on the molecular changes that accompany very early responses to mating and present candidate genes and microRNAs that can be further examined for their participation in alterations of the reproductive tract microenvironment in response to signals from the male.
2023-06-27 | GSE216084 | GEO
Project description:The female’s reproductive tract is exposed directly to the male’s ejaculate, making it a hotspot for mating-induced responses shortly after mating. In Drosophila melanogaster, changes in the reproductive tract are essential to optimize fertilization. To detect the earliest gene regulatory events that underlie these changes, we measured transcript abundances using RNA-seq and microRNA-seq of reproductive tracts of unmated females and females collected within 10-15 minutes after the end of mating, either to a wildtype male or to a male with defective BMP signaling in secondary cells of the accessory gland, which influences the composition of the male’s ejaculate. We observed transcript abundance changes for genes with roles in tissue morphogenesis, wound healing, the immune response and metabolism. Strikingly, predicted targets of microRNAs that respond to mating are enriched for overlapping functions, suggesting that mating-induced changes are in part regulated by microRNAs. Most of the differentially expressed RNAs are upregulated in response to mating, while most of the differentially expressed microRNAs are downregulated. This pattern suggests a response of activation and de-repression of gene programs that switch the reproductive tract to a “mated” state, rather than a repression of virgin-specific programs. Male genotype did not influence transcript levels, indicating that the earliest transcriptomic responses in the reproductive tract are not dependent on ejaculate components that require BMP signaling in secondary cells. Our results shed light on the molecular changes that accompany very early responses to mating and present candidate genes and microRNAs that can be further examined for their participation in alterations of the reproductive tract microenvironment in response to signals from the male.
2023-06-27 | GSE216083 | GEO
Project description:Sexual reproduction can promote genetic diversity in eukaryotes, and yet many pathogenic fungi have been labeled as obligate asexual species. It is becoming increasingly clear, however, that cryptic sexual programs may exist in some species, and that efficient mating requires the necessary developmental switch to be triggered. In this study we investigate Candida tropicalis, an important human fungal pathogen that has been reported to be asexual. Significantly, we demonstrate that C. tropicalis uses a phenotypic switch to regulate a cryptic program of sexual mating. Thus, diploid a and α cells must undergo a developmental transition to the mating-competent form, and only then does efficient cell-cell conjugation take place resulting in the formation of stable a/α tetraploids. We show that both the phenotypic switch and sexual mating depend on the conserved transcriptional regulator Wor1, which is regulated by temperature in other fungal species. In contrast, C. tropicalis mating occurs efficiently at both 25 °C and 37 °C, suggesting that it could occur in the mammalian host and have direct consequences for the outcome of an infection. Transcriptional profiling further reveals that ≈400 genes are differentially expressed between the two phenotypic states, including the regulatory factor Wor1. Taken together, our results demonstrate that C. tropicalis has a unique sexual program, and that entry to this program is controlled via a Wor1-mediated, metastable switch. These observations have direct implications for the regulation and evolution of cryptic sexual programs in related fungal pathogens.
2012-08-28 | GSE40179 | GEO
Project description:Velvet domain proteins coordinate developmental processes and secondary metabolism in fungi. In this study, we characterized the role of all four velvet proteins in the life cycle of the plant pathogenic fungus Verticillium dahliae. From other fungi, the formation of different homo-and heterodimers as well as complexes with non-velvet proteins is known. We could show that V. dahliae Vel1 is important for initial plant root colonization. In planta, Vel1 together with Vel3 is involved in fungal distribution by conidia. Disease symptom induction in tomato plants also depends on Vel1. In the senescent plant formation of microsclerotia as resting structure ex planta is controlled by Vel1, Vel2 and Vel3. In vitro protein pull-downs were conducted to identify interaction partners of velvet proteins in V. dahliae. In this study, we were able to identify interactions between Vel1 and Vel2, Vel2 and Vos1, and Vel3 and Vos1 during vegetative hyphae growth, respectively. Similar interactions are known for A. nidulans. Further interacting candidates were identified for the velvet proteins except for Vel3, for which only interaction with Vos1 was found during the tested conditions. Velvet-interacting candidate proteins included redox-regulating proteins and metabolic enzymes, but also proteins involved in energy metabolism and transport.
2021-02-23 | PXD021861 | Pride
Project description:In adult mammals, skin wound healing has evolved to favor rapid repair through the formation of fibrotic scar. These dermal scars are dysfunctional and may lead to chronic disfigurement and disability, yet the biologic mechanisms that drive fibrosis and prevent tissue regeneration remain unknown. Here, we report that reindeer (Rangifer tarandus) antler velvet exhibits regenerative wound healing, whereas identical full-thickness injury in dorsal back skin of the same animal forms fibrotic scar. This regenerative capacity is retained even following ectopic transplantation of velvet to a scar-forming site, demonstrating that this latent regenerative capacity is innate to velvet cells and independent of local factors derived from the growing antler. Single cell RNA-sequencing of uninjured skin revealed a marked divergence in resting fibroblast transcriptional states and immunomodulatory function. Uninjured velvet fibroblast shared a striking resemblance with human fetal fibroblasts whereas uninjured back skin fibroblasts exhibited an overrepresentation of pro-inflammatory genes resembling adult human fibroblasts. Identical skin injury resulted in site-specific fibroblast polarization; back fibroblasts exacerbated the inflammatory response, whereas velvet fibroblasts adopted an immunosuppressive state and reverted back to a regeneration-competent ground state. Consequently, velvet wounds exhibited an accelerated adoption of anti-inflammatory immune states and an expedited resolution of immune response. This study demonstrates reindeer as a novel comparative mammalian model to study both adult skin regeneration (velvet) and scar formation (back skin) within the same animal. Our study underscores the importance of fibroblast heterogeneity in shaping local immune cell functions that ultimately polarize wound healing outcomes. Purposeful, acute modulation of fibroblast-mediated immune signaling represents an important therapeutic avenue to mitigate scar and improve wound healing.
2022-12-08 | GSE207021 | GEO