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

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. Wyspianska, Gosia Trynka, David F. Tough, Andrew Bassett, Daniel J. Gaffney (), Damiana Alvarez-Errico () and Roser Vento-Tormo ()
Additional contact information
Clara Alsinet: Wellcome Genome Campus
Maria Nascimento Primo: Wellcome Genome Campus
Valentina Lorenzi: Wellcome Genome Campus
Erica Bello: 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
Gosia Trynka: Wellcome Genome Campus
David F. Tough: Medicines Research Centre, GlaxoSmithKline
Andrew Bassett: Wellcome Genome Campus
Daniel J. Gaffney: Wellcome Genome Campus
Damiana Alvarez-Errico: Josep Carreras Leukaemia Research Institute (IJC)
Roser Vento-Tormo: Wellcome Genome Campus

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30557-4

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DOI: 10.1038/s41467-022-30557-4

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