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In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming

ABSTRACT: In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming

PROVIDER: PRJNA923617 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23073465_1.fastq.gz	Fastqsanger.gz
	SRR23073465_2.fastq.gz	Fastqsanger.gz
	SRR23073466_1.fastq.gz	Fastqsanger.gz
	SRR23073466_2.fastq.gz	Fastqsanger.gz
	SRR23073467_1.fastq.gz	Fastqsanger.gz

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In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming

Project description:Sexual reproduction of Toxoplasma gondii, which is restricted to the small intestine of felids, is sparsely documented in studies involving domestic cats, which also raises ethical concerns. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. Here we show that AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites, as revealed by mass spectrometry-based proteomic analyses of the parasites.

2023-09-16 | PXD039400 | Pride

In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming [ATAC-seq]

Project description:In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming [ATAC-seq]

| PRJNA923619 | ENA

In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming [ChIP-seq]

Project description:In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming [ChIP-seq]

| PRJNA923616 | ENA

In vitro production of cat-restricted Toxoplasma pre-sexual stages.

Project description:Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described1,2. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. 1), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.

| S-EPMC10781626 | biostudies-literature

In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming [ATAC-seq]

Project description:Here we show that AP2XII-1 and AP2XI-2, two transcription factors expressed in tachyzoites, a stage that causes acute toxoplasmosis, silence genes specific to merozoites, a developmental stage critical for sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a drastic change in the transcriptional program, promoting a complete transition from tachyzoites to merozoites. Pre-gametes produced in vitro are characterized by specific protein markers and undergo typical asexual endopolygenic division cycles. AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit the epigenitors MORC and HDAC3, which in turn restrict the accessibility of chromatin to the transcriptional machinery.

2023-09-16 | GSE222832 | GEO

In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming [ChIP-seq]

2023-09-16 | GSE222819 | GEO

In vitro production of cat-restricted Toxoplasma pre-sexual stages by epigenetic reprogramming

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-16 | GSE222835 | GEO

Transcriptomics of Toxoplasma gondii enteroepithelial stages

Project description:Toxoplasma gondii is a zoonotic pathogen for which felids serve as definitive hosts. In cats, the parasite undergoes several rounds of asexual replication before entering the sexual cycle which gives rise to oocysts that are shed into the environment. These then sporulate and become infective to humans and live stock. To understand the genes involved in the parasite development in the felid host and identify potential intervention targets, we designed a transcriptomic approach to compare the cat intestinal stages with the well characterised tachyzoites that mediate acute infection and tissue cysts that are responsible for chronic infection. Cats were infected with T. gondii tissue cysts from mouse brain and sampled the intestinal stages at day 3, 5 and 7 post infection. As an input sample, we also collected tissue cysts from mouse brain as well as in vitro cultivated tachyzoites. Total RNA was extracted, enriched for mRNA and used for cDNA synthesis. RNA-Seq was then performed to describe the transcriptomic repertoire of each time point/life cycle stage.

2018-03-30 | GSE108740 | GEO

A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment

Project description:Purpose: T. gondii has a complex life cycle typified by an asexual development taking place in vertebrate and a sexual reproduction occurring exclusively in felids and thereby is less studied. The developmental transitions rely on changes in gene expression patterns, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific programs for a given stage. Here, we identified T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in partnership with Apetala (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the chromatin accessibility of the genes predestined to be exclusively expressed in sexual stages. As such, MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, thus revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 factors, with these latter potentially contributing to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a way to study the parasite’s sexual development in vitro, and proposes an alternative to the requirement of cat infections.

2019-12-21 | GSE136123 | GEO

A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment

Project description:Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.

2019-12-21 | GSE136060 | GEO

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