RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA608012 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11142813.fastq.gz | Fastqsanger.gz | |||
| SRR11142814.fastq.gz | Fastqsanger.gz | |||
| SRR11142815.fastq.gz | Fastqsanger.gz | |||
| SRR11142816.fastq.gz | Fastqsanger.gz | |||
| SRR11142817.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 35 |
Similar Datasets
Project description:The apicomplexan parasites Plasmodium spp. are the causative agents of malaria, a disease that poses a significant global health burden. Plasmodium spp. initiate infection of the human host by transforming and replicating within hepatocytes. Yet, despite the liver stage being a critical step during infection, most transcriptomic studies have focused on more technically accessible stages of the Plasmodium life cycle, limiting our ability to target these parasites to prevent disease. We have conducted an extensive RNA-seq analysis of the Plasmodium berghei liver stage at high-resolution, covering early (2—18 hpi) and mid-stages (24—48 hpi) of the liver stage of infection. Our data revealed hundreds of genes are differentially expressed as early as 2 hours post-infection, and that multiple genes shown to be important for later infection may be upregulated as early as 12 hpi. Using hierarchical clustering along with co-expression analysis, we identified clusters functionally enriched for important liver-stage processes such as interactions with the host cell and redox homeostasis. Furthermore, some of these clusters were highly correlated to the expression of ApiAP2 transcription factors, while showing enrichment of mostly uncharacterized DNA binding motifs hinting at alternative uncharacterized targets during this stage. Our work represents a window into the previously undescribed transcriptome of the early LS upon host cell infection and offers a comprehensive view of the Plasmodium liver stage. Using the tractable organism P. berghei, our dataset provides a blueprint for future studies in the human-infective parasites, P. falciparum and P. vivax.
2020-02-22 | GSE145731 | GEO
Project description:The apicomplexan parasites Plasmodium spp. are the causative agents of malaria, a disease that poses a significant global health burden. Plasmodium spp. initiate infection of the human host by transforming and replicating within hepatocytes. This liver stage (LS) is poorly understood compared to other Plasmodium life stages, which has hindered our ability to target these parasites for disease prevention. We conducted an extensive transcriptome sequencing (RNA-Seq) analysis throughout the Plasmodium berghei LS, covering as early as 2 h postinfection (hpi) and extending to 48 hpi. Our data revealed that hundreds of genes are differentially expressed at 2 hpi and that multiple genes shown to be important for later infection are upregulated as early as 12 hpi. Using hierarchical clustering along with coexpression analysis, we identified clusters functionally enriched for important liver-stage processes such as interactions with the host cell and redox homeostasis. Furthermore, some of these clusters were highly correlated to the expression of ApiAP2 transcription factors, while showing enrichment of mostly uncharacterized DNA binding motifs. This finding indicates potential LS targets for these transcription factors, while also hinting at alternative uncharacterized DNA binding motifs and transcription factors during this stage. Our work presents a window into the previously undescribed transcriptome of Plasmodium upon host hepatocyte infection to enable a comprehensive view of the parasite's LS. These findings also provide a blueprint for future studies that extend hypotheses concerning LS gene function in P. berghei to human-infective Plasmodium parasites.IMPORTANCE The LS of Plasmodium infection is an asymptomatic yet necessary stage for producing blood-infective parasites, the causative agents of malaria. Blocking the liver stage of the life cycle can prevent clinical malaria, but relatively less is known about the parasite's biology at this stage. Using the rodent model P. berghei, we investigated whole-transcriptome changes occurring as early as 2 hpi of hepatocytes. The transcriptional profiles of early time points (2, 4, 12, and 18 hpi) have not been accessible before due to the technical challenges associated with liver-stage infections. Our data now provide insights into these early parasite fluxes that may facilitate establishment of infection, transformation, and replication in the liver.
| S-EPMC7002348 | biostudies-literature
Project description:Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages
2017-08-21 | GSE102167 | GEO
Project description:Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Yet, the underlying mechanisms driving the pathogenesis of malaria-associated hypoglycemia remain poorly understood. Here we report that labile heme, an alarmin generated as a byproduct of hemolysis during the blood stage of Plasmodium spp. infection, plays a central role in the development of malaria-associated hypoglycemia. Labile heme recapitulated the hypometabolic response to Plasmodium (chabaudi chabaudi; Pcc) infection in mice, including the development of anorexia, transcriptional repression of hepatic glucose production (HGP) and reduction of glycemia, energy expenditure (EE) as well as core body temperature. While this hypometabolic response is protective against immune-mediated liver damage and anemia, when sustained over time it can lead to hypoglycemia and compromise EE as well as thermoregulation. In response, asexual stages of Plasmodium spp. activate a transcriptional program that reduces virulence in favor of sexual commitment and presumably malaria transmission. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic defense strategy against Plasmodium infection.
2021-12-31 | E-MTAB-10935 | biostudies-arrayexpress
Project description:Determination of gene expression level changes of whole genome during Plasmodium falciparum development in early liver stage (at 24h and 48h), compared to mixed blood stage and sporozoite stage. A set of Genes selected from this expression analysis are further verified by qPCR and a sub-set were tested for their vaccine efficacy. 6 genomic tiling arrays: 3 time points in early liver infection (spz, hr24, hr48), and 3 blood stage isolates
2014-07-01 | E-GEOD-56959 | biostudies-arrayexpress
Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 µM), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.
2011-10-31 | GSE32485 | GEO
Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 M-BM-5M), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms. Genome DNA from IP resistant strains vs. Reference 3D7 or Dd2
2011-10-31 | E-GEOD-32485 | biostudies-arrayexpress
Project description:Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified more than 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.
2023-08-02 | GSE199239 | GEO
Project description:Development of Plasmodium falciparum liver stages in human fetal hepatocyte organoid cultures
| PRJNA819014 | ENA
Project description:Phosphatase type 1 is a major enzyme essential to Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. In this work, we report the functional characterization of the Plasmodium berghei LRR1, an ortholog of SDS22, one of the most ancient and conserved Phosphatase type 1 (PP1) interactor. SDS22 has been described as a PP1 regulator essential to critical cellular features such as motility, polarity, epithelium integrity or mitosis completion. Our study shows that in Plasmodium berghei, PbLRR1 is expressed during the intra-erythrocytic developmental cycle and up to the zygote stage during sexual development. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and is able to inhibit the phosphatase activity. Then, genetic analysis demonstrated that PbLRR1 deletion affects the course of the parasite development during early sporogony which manifest by the production of fewer and smaller oocysts. Finally, PbLRR1 interactome analysis associated with phospho-proteomics studies led to the identification of several putative PbLRR1/PbPP1 substrates. Although previously unsuspected PP1 substrates, some of them have been characterized as essential to the parasite sexual development. In addition, and for the first time, we identify the PP1 inhibitor 3 as a substrate of the PP1/LRR1 complex. In summary, this study provides insights into previously unrecognized PbPP1 fine regulation of Plasmodium early sporogony development through its interaction with PbLRR1.
2022-10-14 | PXD030389 | Pride