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Single-cell RNA-seq...
Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria
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Lönnberg, Tapio (author)
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Svensson, Valentine (author)
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James, Kylie R. (author)
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show more...
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Fernandez-Ruiz, Daniel (author)
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Sebina, Ismail (author)
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Montandon, Ruddy (author)
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Soon, Megan S. F. (author)
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Fogg, Lily G. (author)
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Nair, Arya Sheela (author)
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Liligeto, Urijah (author)
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Stubbington, Michael J. T. (author)
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Ly, Lam-Ha (author)
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Bagger, Frederik Otzen (author)
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Zwiessele, Max (author)
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Lawrence, Neil D. (author)
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Souza-Fonseca-Guimaraes, Fernando (author)
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Bunn, Patrick T. (author)
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Engwerda, Christian R. (author)
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Heath, William R. (author)
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- Billker, Oliver (author)
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, U.K.
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Stegle, Oliver (author)
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Haque, Ashraful (author)
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Teichmann, Sarah A. (author)
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Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2017
- 2017
- English.
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In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 2:9
- Related links:
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https://research-rep...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Differentiation of naïve CD4(+) T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Lönnberg, Tapio
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Svensson, Valent ...
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James, Kylie R.
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Fernandez-Ruiz, ...
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Sebina, Ismail
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Montandon, Ruddy
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show more...
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Soon, Megan S. F ...
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Fogg, Lily G.
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Nair, Arya Sheel ...
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Liligeto, Urijah
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Stubbington, Mic ...
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Ly, Lam-Ha
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Bagger, Frederik ...
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Zwiessele, Max
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Lawrence, Neil D ...
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Souza-Fonseca-Gu ...
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Bunn, Patrick T.
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Engwerda, Christ ...
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Heath, William R ...
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Billker, Oliver
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Stegle, Oliver
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Haque, Ashraful
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Teichmann, Sarah ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Science immunolo ...
- By the university
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Umeå University