RNA-Seq assay identifies potential regulon and downstream targets of Msd1 under mating-inducing and -repressing conditions in a global basidiomycete pathogen
Ontology highlight
ABSTRACT:
ORGANISM(S): Cryptococcus deneoformans
PROVIDER: GSE308021 | GEO | 2026/06/11
REPOSITORIES: GEO
Similar Datasets
Project description:In the human fungal pathogen Cryptococcus neoformans, sexual mating is considered to benefit its infections through meiosis-driven hyper-virulent variants and infectious meiotic spores. How meiotic cycle and mating differentiation program are genetically and developmentally integrated to safeguard successful meiotic sporulation remains poorly known. In C. neoformans, sporulation occurs following two parallel events, meiosis and differentiation of specialized cell termed basidium. To reveal the gene circuits specifically orchestrating basidial maturation and meiosis, we performed high-coverage stand-specific RNA-sequencing analysis to monitor gene induction timing through unisexual differentiation and reveals a co-regulation of these two events by a shared regulatory program. Our findings indicated that the regulatory coupling of meiosis and basidial development may serve as a determinant underlying production of infectious meiospores in C. neoformans.
2018-11-14 | GSE111975 | GEO
Project description:Sexual development is a fundamental process that promotes infection and the emergence of highly virulent and drug-resistant isolates in the human fungal pathogen Cryptococcus neoformans. While the genetic factors involved in sexual life cycle have been extensively investigated in this pathogenic fungus, the critical regulator(s) beyond transcriptional machinery remains poorly understood. Rei1, a conserved C2H2-type zinc finger protein, functions as a 60S ribosome biogenesis factor and plays a crucial role in maintaining cellular growth at low temperature in yeast. In this study, we identified a yeast Rei1-like protein, Rel1, based on its encoding gene that was dynamically up-regulated during unisexual reproduction in C. neoformans. Similar to Rei1’s role in yeast, disruption of REL1 gene results in significant growth retardation under low temperature conditions. Consistent with its upregulation during sexual development, REL1 deletion compromised the entire sexual cycle, including yeast-hyphae morphogenesis, basidial differentiation, meiosis and sporulation. RNA-Seq analysis revealed that Rei1 is required for the transcriptional activation of key sexual reproduction gene sets involved in mating response, morphogenesis and meiosis, suggesting a potential link between ribosome biogenesis and sexual development in C. neoformans. Furthermore, REL1 disruption increased susceptibility to the antifungal drug 5’-flucytosine (5’-FC) but enhanced resistance to fluconazole, indicating its differential role in antifungal drugs resistance mechanisms. Collectively, this study provides critical insights into how C. neoformans utilize a conserved ribosome biogenesis factor to coordinate cold resistance, sexual development, and antifungal susceptibility, highlighting both conserved and divergent functions of this C2H2 zinc-finger protein compared to its ortholog in budding yeast.
2025-11-11 | GSE296246 | GEO
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:Ray2013 - Meiotic initiation in S. cerevisiae
A mathematical representation of early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signalling molecules for regulating protein activities, is described here
This model is described in the article:
Dynamic modeling of yeast meiotic initiation.
Ray D, Su Y, Ye P.
BMC Syst Biol. 2013 May 1;7:37
Abstract:
BACKGROUND:
Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genetic backgrounds. To investigate signal transduction pathways that regulate transient protein expression and sporulation efficiency, we develop a mathematical model using ordinary differential equations. The model describes early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signaling molecules for regulating protein activities.
RESULTS:
The mathematical model is capable of simulating the orderly and transient dynamics of meiotic proteins including Ime1, the master regulator of meiotic initiation, and Ime2, a kinase encoded by an early gene. The model is validated by quantitative sporulation phenotypes of single-gene knockouts. Thus, we can use the model to make novel predictions on the cooperation between proteins in the signaling pathway. Virtual perturbations on feedback loops suggest that both positive and negative feedback loops are required to terminate expression of early meiotic proteins. Bifurcation analyses on feedback loops indicate that multiple feedback loops are coordinated to modulate sporulation efficiency. In particular, positive auto-regulation of Ime2 produces a bistable system with a normal meiotic state and a more efficient meiotic state.
CONCLUSIONS:
By systematically scanning through feedback loops in the mathematical model, we demonstrate that, in yeast, the decisions to terminate protein expression and to sporulate at different efficiencies stem from feedback signals toward the master regulator Ime1 and the early meiotic protein Ime2. We argue that the architecture of meiotic initiation pathway generates a robust mechanism that assures a rapid and complete transition into meiosis. This type of systems-level regulation is a commonly used mechanism controlling developmental programs in yeast and other organisms. Our mathematical model uncovers key regulations that can be manipulated to enhance sporulation efficiency, an important first step in the development of new strategies for producing gametes with high quality and quantity.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000626
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000626 | BioModels
Project description:Many fungi form complex three-dimensional fruiting bodies, within which the meiotic machinery for sexual spore production has been considered to be largely conserved over evolutionary time. Indeed, much of what we know about meiosis in plant and animal taxa has been deeply informed by studies of meiosis in Saccharomyces and Neurospora. Nevertheless, the genetic basis of fruiting body development and its regulation in relation to meiosis in fungi is barely known, even within the best studied multicellular fungal model Neurospora crassa. We characterized morphological development and genome-wide transcriptomics in the closely related species Neurospora crassa, Neurospora tetrasperma, and Neurospora discreta, across eight stages of sexual development. Despite diverse life histories within the genus, all three species produce vase-shaped perithecia. Transcriptome sequencing provided gene expression levels of 2479 orthologous genes among all three species. Expression of key meiosis genes and sporulation genes, corresponded to developmental differences among these Neurospora species during sexual development. Screening N. crassa knockout crosses of genes selected for their expression differences across species, eight genes, whose functions were previously unknown, are found to be critical for the successful formation of perithecia. The absence of these genes in mutant crosses resulted in either no perithecium formation or in arrested development at an early stage. Our results provide insight into the genetic basis of Neurospora sexual reproduction, which is also of great importance with regard to other multicelluar ascomycetes, including fungal pathogens closely related to Neurospora in the Sordariomycetes, such as Fusarium spp, Magnaporthe oryzae, and Nectria haematococca mRNA were sampled and compared from eight time points across sexual reproduction in three Neurospora species
2014-12-12 | E-GEOD-60256 | biostudies-arrayexpress
Project description:Many fungi form complex three-dimensional fruiting bodies, within which the meiotic machinery for sexual spore production has been considered to be largely conserved over evolutionary time. Indeed, much of what we know about meiosis in plant and animal taxa has been deeply informed by studies of meiosis in Saccharomyces and Neurospora. Nevertheless, the genetic basis of fruiting body development and its regulation in relation to meiosis in fungi is barely known, even within the best studied multicellular fungal model Neurospora crassa. We characterized morphological development and genome-wide transcriptomics in the closely related species Neurospora crassa, Neurospora tetrasperma, and Neurospora discreta, across eight stages of sexual development. Despite diverse life histories within the genus, all three species produce vase-shaped perithecia. Transcriptome sequencing provided gene expression levels of 2479 orthologous genes among all three species. Expression of key meiosis genes and sporulation genes, corresponded to developmental differences among these Neurospora species during sexual development. Screening N. crassa knockout crosses of genes selected for their expression differences across species, eight genes, whose functions were previously unknown, are found to be critical for the successful formation of perithecia. The absence of these genes in mutant crosses resulted in either no perithecium formation or in arrested development at an early stage. Our results provide insight into the genetic basis of Neurospora sexual reproduction, which is also of great importance with regard to other multicelluar ascomycetes, including fungal pathogens closely related to Neurospora in the Sordariomycetes, such as Fusarium spp, Magnaporthe oryzae, and Nectria haematococca mRNA were sampled and compared from eight time points across sexual reproduction in three Neurospora species
2014-12-12 | E-GEOD-60255 | biostudies-arrayexpress
Project description:Meiosis was compared in msh5-22 and wild type strains of C. cinerea at 6 time points spanning the meiotic timecourse. Abstract: The basidiomycete Coprinopsis cinerea is well-suited to studies of meiosis because meiosis progresses synchronously in ten million cells within each mushroom cap. Approximately 20% of C. cinerea genes exhibit changing expression during meiosis, but meiosis and mushroom development happen concurrently so differentially expressed genes might not be directly involved in meiotic processes. Using microarrays, we examined global gene expression across a meiotic time course in two mutants in which meiosis arrests but mushrooms develop normally. Genes differentially expressed in the mutants compared to wild type are likely to be involved in meiosis and sporulation as opposed to mushroom development. In rad50-1, which arrests in late prophase, RNA abundance for a group of early meiotic genes remains high, while the expression of a group of late meiotic genes is never induced. In contrast, in msh5-22 (which fails to undergo pre-meiotic DNA replication), both early and late meiotic genes are underexpressed relative to wild type at late meiotic time points as the cells die. Genes that are differentially expressed in both mutants are particularly strong candidates for playing roles in meiosis and sporulation.
2012-05-15 | GSE37943 | GEO
Project description:Meiosis was compared in rad50-1 and wild type strains of C. cinerea at 6 time points spanning the meiotic timecourse. Abstract: The basidiomycete Coprinopsis cinerea is well-suited to studies of meiosis because meiosis progresses synchronously in ten million cells within each mushroom cap. Approximately 20% of C. cinerea genes exhibit changing expression during meiosis, but meiosis and mushroom development happen concurrently so differentially expressed genes might not be directly involved in meiotic processes. Using microarrays, we examined global gene expression across a meiotic time course in two mutants in which meiosis arrests but mushrooms develop normally. Genes differentially expressed in the mutants compared to wild type are likely to be involved in meiosis and sporulation as opposed to mushroom development. In rad50-1, which arrests in late prophase, RNA abundance for a group of early meiotic genes remains high, while the expression of a group of late meiotic genes is never induced. In contrast, in msh5-22 (which fails to undergo pre-meiotic DNA replication), both early and late meiotic genes are underexpressed relative to wild type at late meiotic time points as the cells die. Genes that are differentially expressed in both mutants are particularly strong candidates for playing roles in meiosis and sporulation.
2012-05-15 | GSE37942 | GEO
Project description:Ray2013 - S.cerevisiae meiosis-specific metabolic network
Meiosis is a strongly concerved cell division program that generates haploid gametes from a diploid parental cell. Successful meiosis is the fundamental basis of sexual reproduction. Multiple lines of evidence suggest a tight link between meiosis and metabolism. Here, yeast meiosis is studied to elucidate the link between reproduction and metabolism. Network flux is obtained using GLPK (GNU Linear Programming Kit) supported by the COBRA Toolbox for Matlab.
This model is described in the article:
Characterization of the metabolic requirements in yeast meiosis.
Ray D, Ye P.
PLoS One. 2013 May 8;8(5):e63707.
Abstract:
The diploid yeast Saccharomyces cerevisiae undergoes mitosis in glucose-rich medium but enters meiosis in acetate sporulation medium. The transition from mitosis to meiosis involves a remarkable adaptation of the metabolic machinery to the changing environment to meet new energy and biosynthesis requirements. Biochemical studies indicate that five metabolic pathways are active at different stages of sporulation: glutamate formation, tricarboxylic acid cycle, glyoxylate cycle, gluconeogenesis, and glycogenolysis. A dynamic synthesis of macromolecules, including nucleotides, amino acids, and lipids, is also observed. However, the metabolic requirements of sporulating cells are poorly understood. In this study, we apply flux balance analyses to uncover optimal principles driving the operation of metabolic networks over the entire period of sporulation. A meiosis-specific metabolic network is constructed, and flux distribution is simulated using ten objective functions combined with time-course expression-based reaction constraints. By systematically evaluating the correlation between computational and experimental fluxes on pathways and macromolecule syntheses, the metabolic requirements of cells are determined: sporulation requires maximization of ATP production and macromolecule syntheses in the early phase followed by maximization of carbohydrate breakdown and minimization of ATP production in the middle and late stages. Our computational models are validated by in silico deletion of enzymes known to be essential for sporulation. Finally, the models are used to predict novel metabolic genes required for sporulation. This study indicates that yeast cells have distinct metabolic requirements at different phases of meiosis, which may reflect regulation that realizes the optimal outcome of sporulation. Our meiosis-specific network models provide a framework for an in-depth understanding of the roles of enzymes and reactions, and may open new avenues for engineering metabolic pathways to improve sporulation efficiency.
This model is hosted on BioModels Database
and identified
by: MODEL1303140001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2005-01-01 | MODEL1303140001 | BioModels
Project description:Mating pheromone is the best-known fungal paracrine signal whose essentiality in determining sexual reproduction has been recognized since six decades ago. We demonstrate that the pheromone cannot induce mating response during unisexual mating due to the lack of a compatible receptor from the same unisexual population. We identify a quorum sensing (QS) peptide Qsp1 in place of pheromone as a specific intercellular signal directing Cryptococcus unisexual reproduction. A typical zinc finger regulator Cqs2 as the master regulator of QS signaling induces unisexual reproduction in response to Qsp1. Collectively, these data demonstrate that QS activation rather than pheromone induction as the pivotal social control mechanism underlies unisexual reproduction in C .neoformans.
2018-05-15 | GSE94091 | GEO