Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing

Briggs, E. M., Rojas, F., McCulloch, R. , Matthews, K. R. and Otto, T. D. (2021) Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing. Nature Communications, 12, 5268. (doi: 10.1038/s41467-021-25607-2) (PMID:34489460) (PMCID:PMC8421343)

[img] Text
251120.pdf - Published Version
Available under License Creative Commons Attribution.

8MB

Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Briggs, Miss Emma and McCulloch, Professor Richard and Rojas, Mr Federico and Otto, Dr Thomas
Creator Roles:
Briggs, E. M.Methodology, Data curation
Rojas, F.Methodology, Data curation
McCulloch, R.Methodology
Otto, T. D.Methodology
Authors: Briggs, E. M., Rojas, F., McCulloch, R., Matthews, K. R., and Otto, T. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Communications 12: 5268
Publisher Policy:Reproduced under a Creative Commons License
Related URLs:
Data DOI:10.5281/zenodo.5163554

University Staff: Request a correction | Enlighten Editors: Update this record