Single-cell RNA-seq and computational analysis using temporal mixture modeling resolves T H 1/T FH fate bifurcation in malaria
Year: 2017
Type: article
Abstract: 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.
Source: Science Immunology
Authors: Tapio Lönnberg, Valentine Svensson, Kylie R. James, Daniel Fernandez-Ruiz, Ismail Sebina, Ruddy Montandon, Megan S. F. Soon, Lily G. Fogg, Arya Sheela Nair, Urijah N. Liligeto, Michael J. T. Stubbington, Lam-Ha Ly, Frederik Otzen Bagger, Max Zwiessele, Neil D. Lawrence, Fernando Souza-Fonseca-Guimaraes, Patrick T. Bunn, Christian R. Engwerda, William R. Heath, Oliver Billker, Oliver Stegle, Ashraful Haque, Sarah A. Teichmann
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2594807826