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Exploring parasite heterogeneity using single-cell RNA-seq reveals a gene signature among sexual stage Plasmodium falciparum parasites
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Number of Authors: 82018 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 371, no 1, p. 130-138Article in journal (Refereed) Published
Abstract [en]

The malaria parasite has a complex lifecycle, including several events of differentiation and stage progression, while actively evading immunity in both its mosquito and human hosts. Important parasite gene expression and regulation during these events remain hidden in rare populations of cells. Here, we combine a capillary-based platform for cell isolation with single-cell RNA-sequencing to transcriptionally profile 165 single infected red blood cells (iRBCs) during the intra-erythrocytic developmental cycle (IDC). Unbiased analyses of single-cell data grouped the cells into eight transcriptional states during IDC. Interestingly, we uncovered a gene signature from the single iRBC analyses that can successfully discriminate between developing asexual and sexual stage parasites at cellular resolution, and we verify five, previously undefined, gametocyte stage specific genes. Moreover, we show the capacity of detecting expressed genes from the variable gene families in single parasites, despite the sparse nature of data. In total, the single parasite transcriptomics holds promise for molecular dissection of rare parasite phenotypes throughout the malaria lifecycle.

Place, publisher, year, edition, pages
2018. Vol. 371, no 1, p. 130-138
Keywords [en]
Malaria, Plasmodium falciparum, Parasites, Single-cell RNA-seq, Transcriptomics, Gametocyte signature, Single-parasite picking
National Category
Biological Sciences Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-161175DOI: 10.1016/j.yexcr.2018.08.003ISI: 000444661200012PubMedID: 30096287OAI: oai:DiVA.org:su-161175DiVA, id: diva2:1261721
Available from: 2018-11-08 Created: 2018-11-08 Last updated: 2018-11-08Bibliographically approved

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Ankarklev, Johan
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Department of Molecular Biosciences, The Wenner-Gren Institute
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