ArticlePLoS genetics2016
A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Transcriptomic atlas throughout Coccidioides development reveals key phase-enriched transcripts of this important fungal pathogen.PLoS biology · 2025Article
- Transcriptomic atlas of the morphologic development of the fungal pathogenbioRxiv : the preprint server for biology · 2024Article
- Do morphogenetic switching and intraspecies variation enhance virulence of Candida auris?PLoS pathogens · 2024Review
- Inducible plasmid copy number control for synthetic biology in commonly used E. coli strains.Nature communications · 2022Article
- Article
- Intraspecies Transcriptional Profiling Reveals Key Regulators of Candida albicans Pathogenic Traits.mBio · 2021Article
- Population genomics of the pathogenic yeast Candida tropicalis identifies hybrid isolates in environmental samples.PLoS pathogens · 2021Article
- The Roles of Chromatin Accessibility in Regulating theJournal of fungi (Basel, Switzerland) · 2021Review
- Parasexuality ofFrontiers in cellular and infection microbiology · 2021Review
- Phase separation and cell fate in Candida.Nature microbiology · 2020Article
- An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation inGenetics · 2020Article
- Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum.PLoS biology · 2019Article
- Genetic Modification of Closely RelatedFrontiers in microbiology · 2019Article
- Exploring intermediate cell states through the lens of single cells.Current opinion in systems biology · 2018Article
- A coupled process of same- and opposite-sex mating generates polyploidy and genetic diversity in Candida tropicalis.PLoS genetics · 2018Article
- Epigenetic control of pheromone MAPK signaling determines sexual fecundity inProceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.