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• W2528023947 abstract "Abstract Differentiation of naïve CD4 + T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to multiple levels of 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 RNA transcriptomics and computational modelling of temporal mixtures, we reconstructed the developmental trajectories of Th1 and Tfh cell populations during Plasmodium infection in mice at single-cell resolution. These cell fates emerged from a common, highly proliferative and metabolically active precursor. Moreover, by tracking clonality from T cell receptor sequences, we infer that ancestors derived from the same naïve CD4 + T cell can concurrently populate both Th1 and Tfh subsets. We further found that precursor T cells were coached towards a Th1 but not a Tfh fate by monocytes/macrophages. The integrated genomic and computational approach we describe is applicable for analysis of any cellular system characterized by differentiation towards multiple fates. One Sentence Summary Using single-cell RNA sequencing and a novel unsupervised computational approach, we resolve the developmental trajectories of two CD4 + T cell fates in vivo , and show that uncommitted T cells are externally influenced towards one fate by inflammatory monocytes." @default.
• W2528023947 created "2016-10-14" @default.
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• W2528023947 date "2016-09-13" @default.
• W2528023947 modified "2023-10-15" @default.
• W2528023947 title "Temporal mixture modelling of single-cell RNA-seq data resolves a CD4+ T cell fate bifurcation" @default.
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• W2528023947 doi "https://doi.org/10.1101/074971" @default.
• W2528023947 hasPublicationYear "2016" @default.
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