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Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis

Author

Listed:
  • Emmanouil I. Athanasiadis

    (University of Cambridge
    Wellcome Trust Genome Campus
    Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute)

  • Jan G. Botthof

    (University of Cambridge
    Wellcome Trust Genome Campus
    Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute)

  • Helena Andres

    (University of Cambridge)

  • Lauren Ferreira

    (University of Cambridge
    Wellcome Trust Genome Campus
    Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute
    Rhodes University)

  • Pietro Lio

    (University of Cambridge)

  • Ana Cvejic

    (University of Cambridge
    Wellcome Trust Genome Campus
    Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute)

Abstract

The success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence of well-defined cell surface markers specific for diverse progenitor populations. An inherent problem with this approach is that the presence of specific cell surface markers does not directly reflect the transcriptional state of a cell. Here, we used a marker-free approach to computationally reconstruct the blood lineage tree in zebrafish and order cells along their differentiation trajectory, based on their global transcriptional differences. Within the population of transcriptionally similar stem and progenitor cells, our analysis reveals considerable cell-to-cell differences in their probability to transition to another committed state. Once fate decision is executed, the suppression of transcription of ribosomal genes and upregulation of lineage-specific factors coordinately controls lineage differentiation. Evolutionary analysis further demonstrates that this haematopoietic programme is highly conserved between zebrafish and higher vertebrates.

Suggested Citation

  • Emmanouil I. Athanasiadis & Jan G. Botthof & Helena Andres & Lauren Ferreira & Pietro Lio & Ana Cvejic, 2017. "Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02305-6
    DOI: 10.1038/s41467-017-02305-6
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