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Robust temporal map of human in vitro myelopoiesis using single-cell genomics

Author

Listed:
  • Clara Alsinet

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Maria Nascimento Primo

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Valentina Lorenzi

    (Wellcome Genome Campus)

  • Erica Bello

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Iva Kelava

    (Wellcome Genome Campus)

  • Carla P. Jones

    (Wellcome Genome Campus)

  • Roser Vilarrasa-Blasi

    (Wellcome Genome Campus)

  • Carmen Sancho-Serra

    (Wellcome Genome Campus)

  • Andrew J. Knights

    (Wellcome Genome Campus)

  • Jong-Eun Park

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Beata S. Wyspianska

    (Wellcome Genome Campus
    Medicines Research Centre, GlaxoSmithKline)

  • Gosia Trynka

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • David F. Tough

    (Medicines Research Centre, GlaxoSmithKline)

  • Andrew Bassett

    (Wellcome Genome Campus
    Wellcome Genome Campus)

  • Daniel J. Gaffney

    (Wellcome Genome Campus)

  • Damiana Alvarez-Errico

    (Josep Carreras Leukaemia Research Institute (IJC))

  • Roser Vento-Tormo

    (Wellcome Genome Campus)

Abstract

Myeloid cells are central to homeostasis and immunity. Characterising in vitro myelopoiesis protocols is imperative for their use in research, immunotherapies, and understanding human myelopoiesis. Here, we generate a >470K cells molecular map of human induced pluripotent stem cells (iPSC) differentiation into macrophages. Integration with in vivo single-cell atlases shows in vitro differentiation recapitulates features of yolk sac hematopoiesis, before definitive hematopoietic stem cells (HSC) emerge. The diversity of myeloid cells generated, including mast cells and monocytes, suggests that HSC-independent hematopoiesis can produce multiple myeloid lineages. We uncover poorly described myeloid progenitors and conservation between in vivo and in vitro regulatory programs. Additionally, we develop a protocol to produce iPSC-derived dendritic cells (DC) resembling cDC2. Using CRISPR/Cas9 knock-outs, we validate the effects of key transcription factors in macrophage and DC ontogeny. This roadmap of myeloid differentiation is an important resource for investigating human fetal hematopoiesis and new therapeutic opportunities.

Suggested Citation

  • Clara Alsinet & Maria Nascimento Primo & Valentina Lorenzi & Erica Bello & Iva Kelava & Carla P. Jones & Roser Vilarrasa-Blasi & Carmen Sancho-Serra & Andrew J. Knights & Jong-Eun Park & Beata S. Wysp, 2022. "Robust temporal map of human in vitro myelopoiesis using single-cell genomics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30557-4
    DOI: 10.1038/s41467-022-30557-4
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    References listed on IDEAS

    as
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