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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 (författare)
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Svensson, Valentine (författare)
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James, Kylie R. (författare)
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visa fler...
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Fernandez-Ruiz, Daniel (författare)
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Sebina, Ismail (författare)
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Montandon, Ruddy (författare)
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Soon, Megan S. F. (författare)
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Fogg, Lily G. (författare)
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Nair, Arya Sheela (författare)
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Liligeto, Urijah (författare)
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Stubbington, Michael J. T. (författare)
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Ly, Lam-Ha (författare)
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Bagger, Frederik Otzen (författare)
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Zwiessele, Max (författare)
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Lawrence, Neil D. (författare)
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Souza-Fonseca-Guimaraes, Fernando (författare)
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Bunn, Patrick T. (författare)
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Engwerda, Christian R. (författare)
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Heath, William R. (författare)
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- Billker, Oliver (författare)
- Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, U.K.
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Stegle, Oliver (författare)
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Haque, Ashraful (författare)
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Teichmann, Sarah A. (författare)
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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
- Engelska.
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 2:9
- Relaterad länk:
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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
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Cell och molekyl ...
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