A single-cell liver atlas of relapsing human malaria
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ABSTRACT:
PROVIDER: PRJNA810434 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A single-cell liver atlas of relapsing human malaria [Bulk-seq]
| PRJNA810432 | ENA
Project description:A single-cell liver atlas of relapsing human malaria [scRNA-seq]
| PRJNA810174 | ENA
Project description:Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.
2022-02-25 | GSE197458 | GEO
Project description:Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.
2022-02-25 | GSE197409 | GEO
Project description:Single-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations but has not yet been widely applied to single-celled organisms. Transcriptional variation in unicellular malaria parasites from the Plasmodium genus is associated with critical phenotypes including red blood cell invasion and immune evasion, yet transcriptional variation at an individual parasite level has not been examined in depth. Here, we describe the adaptation of a single-cell RNA-sequencing (scRNA-seq) protocol to deconvolute transcriptional variation for more than 500 individual parasites of both rodent and human malaria comprising asexual and sexual life-cycle stages. We uncover previously hidden discrete transcriptional signatures during the pathogenic part of the life cycle, suggesting that expression over development is not as continuous as commonly thought. In transmission stages, we find novel, sex-specific roles for differential expression of contingency gene families that are usually associated with immune evasion and pathogenesis.
2017-02-08 | E-ERAD-611 | biostudies-arrayexpress
Project description:A major obstacle in deciphering the hepatic stage of the malaria parasite has been the challenges associated with culturing the infected hepatocytes through the entire liver stage cycle, including that of the dormant form known as hypnozoites. Primary hepatocytes lose their specialized functions in long-term in vitro culture. Hepatocyte infection represents the first step for clinically silent infection and development of malaria parasite Plasmodium in the liver. Thus this liver stage is an ideal target for development of novel antimalarial drugs and vaccine. However, drug discovery against Plasmodium liver stage is severely hampered by the poor understanding of host-cell and parasites interactions during the liver stage infection and development. In this study, we have performed tandem mass tags (TMT) labelling based quantitative proteomic analysis in simian primary hepatocytes cultured in three different systems of susceptibility to plasmodium infection. Our results represent the first documentation of potentially essential molecular markers including asialoglycoprotein receptor (ASGPR), apolipoproteins, squalene synthase and scavenger receptor B1 (SR-BI) required for productive infection and full development in relapsing Plasmodium species. The identification of these candidate proteins for constructive infection and development of Plasmodium in malaria paves the way to explore them as therapeutic targets.
2019-09-02 | PXD013310 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-25 | GSE197459 | GEO
Project description:Single cell atlas of the mouse foetal liver
| PRJNA746333 | ENA
Project description:To dissect the early aspects of liver haematopoiesis as well as the development of other liver cell lineages we generated a new single cell RNA-seq (scRNA-seq) atlas of the mouse E12.5 liver
2021-08-18 | GSE180050 | GEO
Project description:Liver transcriptomics during malaria
| PRJNA631695 | ENA