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

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...

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Published inNature communications Vol. 12; no. 1; p. 5268
Main Authors Briggs, Emma M., Rojas, Federico, McCulloch, Richard, Matthews, Keith R., Otto, Thomas D.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 06.09.2021
Nature Publishing Group
Nature Portfolio
Subjects
14/1
14/63
38/39
38/62
38/90
38/91
631/114
631/136/142
631/326/417
Animals
Cell cycle
Cell Cycle - genetics
Cell Cycle - physiology
Differentiation
Failure analysis
Gene expression
Gene Expression Regulation
Humanities and Social Sciences
multidisciplinary
Mutation
Parasites
Protozoan Proteins - genetics
Quorum Sensing
Science
Science (multidisciplinary)
Sequence Analysis, RNA - methods
Single-Cell Analysis
Transcriptomes
Trypanosoma brucei
Trypanosoma brucei brucei - cytology
Trypanosoma brucei brucei - genetics
Trypanosoma brucei brucei - physiology
Trypanosome
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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. Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.
AbstractList 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.Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.
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. Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.
Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.
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.
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.
ArticleNumber 5268
Author Matthews, Keith R.
McCulloch, Richard
Rojas, Federico
Briggs, Emma M.
Otto, Thomas D.
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PublicationPlace_xml – name: London
– name: England
PublicationTitle Nature communications
PublicationTitleAbbrev Nat Commun
PublicationTitleAlternate Nat Commun
PublicationYear 2021
Publisher Nature Publishing Group UK
Nature Publishing Group
Nature Portfolio
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
– name: Nature Portfolio
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Snippet Developmental steps in the trypanosome life-cycle involve transition between replicative and non-replicative forms specialised for survival in, and...
Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative...
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SubjectTerms 14/1
14/63
38/39
38/62
38/90
38/91
631/114
631/136/142
631/326/417
Animals
Cell cycle
Cell Cycle - genetics
Cell Cycle - physiology
Differentiation
Failure analysis
Gene expression
Gene Expression Regulation
Humanities and Social Sciences
multidisciplinary
Mutation
Parasites
Protozoan Proteins - genetics
Quorum Sensing
Science
Science (multidisciplinary)
Sequence Analysis, RNA - methods
Single-Cell Analysis
Transcriptomes
Trypanosoma brucei
Trypanosoma brucei brucei - cytology
Trypanosoma brucei brucei - genetics
Trypanosoma brucei brucei - physiology
Trypanosome
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Title Single-cell transcriptomic analysis of bloodstream Trypanosoma brucei reconstructs cell cycle progression and developmental quorum sensing
URI https://link.springer.com/article/10.1038/s41467-021-25607-2
https://www.ncbi.nlm.nih.gov/pubmed/34489460
https://www.proquest.com/docview/2569483217
https://search.proquest.com/docview/2570113198
https://pubmed.ncbi.nlm.nih.gov/PMC8421343
https://doaj.org/article/67a99b605cd74f13ac7108641227f1f1
Volume 12
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