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Lookup NU author(s): Dr Emma BriggsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Developmental steps in the trypanosome life-cycle involve transition between replicative and non-replicative forms specialised for survival in, and transmission between, mammalian and tsetse fly hosts. Here, using oligopeptide-induced differentiation in vitro, we model the progressive development of replicative 'slender' to transmissible 'stumpy' bloodstream form Trypanosoma brucei and capture the transcriptomes of 8,599 parasites using single cell transcriptomics (scRNA-seq). Using this framework, we detail the relative order of biological events during asynchronous development, profile dynamic gene expression patterns and identify putative regulators. We additionally map the cell cycle of proliferating parasites and position stumpy cell-cycle exit at early G1 before progression to a distinct G0 state. A null mutant for one transiently elevated developmental regulator, ZC3H20 is further analysed by scRNA-seq, identifying its point of failure in the developmental atlas. This approach provides a paradigm for the dissection of differentiation events in parasites, relevant to diverse transitions in pathogen biology.
Author(s): Briggs EM, Rojas F, McCulloch R, Matthews KR, Otto TD
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2021
Volume: 12
Online publication date: 06/09/2021
Acceptance date: 17/08/2021
Date deposited: 20/02/2025
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-021-25607-2
DOI: 10.1038/s41467-021-25607-2
Data Access Statement: The transcriptome data generated in this study have been deposited in the European Nucleotide Archive with accession number PRJEB41744. The processed transcript count data and cell metadata generated in this study are available at Zenodo (https://zenodo.org/record/5163554#.YQvu2ZNKjUo)91. Data can be sourced via Supplementary Data Tables and wild-type scRNA-seq data can be explored using the interactive cell atlas (http://cellatlas.mvls.gla.ac.uk/TbruceiBSF/). Source data are provided with this paper. Code used to perform analysis described can be accessed at Zenodo (https://zenodo.org/record/5163554#.YQvu2ZNKjUo)
PubMed id: 34489460
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