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Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors

Author

Listed:
  • Serena Belluschi

    (University of Cambridge)

  • Emily F. Calderbank

    (University of Cambridge)

  • Valerio Ciaurro

    (University of Cambridge)

  • Blanca Pijuan-Sala

    (University of Cambridge)

  • Antonella Santoro

    (University of Cambridge)

  • Nicole Mende

    (University of Cambridge)

  • Evangelia Diamanti

    (University of Cambridge)

  • Kendig Yen Chi Sham

    (University of Cambridge)

  • Xiaonan Wang

    (University of Cambridge)

  • Winnie W. Y. Lau

    (University of Cambridge)

  • Wajid Jawaid

    (University of Cambridge)

  • Berthold Göttgens

    (University of Cambridge)

  • Elisa Laurenti

    (University of Cambridge)

Abstract

Capturing where and how multipotency is lost is crucial to understand how blood formation is controlled. Blood lineage specification is currently thought to occur downstream of multipotent haematopoietic stem cells (HSC). Here we show that, in human, the first lineage restriction events occur within the CD19−CD34+CD38−CD45RA−CD49f+CD90+ (49f+) HSC compartment to generate myelo-lymphoid committed cells with no erythroid differentiation capacity. At single-cell resolution, we observe a continuous but polarised organisation of the 49f+ compartment, where transcriptional programmes and lineage potential progressively change along a gradient of opposing cell surface expression of CLEC9A and CD34. CLEC9AhiCD34lo cells contain long-term repopulating multipotent HSCs with slow quiescence exit kinetics, whereas CLEC9AloCD34hi cells are restricted to myelo-lymphoid differentiation and display infrequent but durable repopulation capacity. We thus propose that human HSCs gradually transition to a discrete lymphoid-primed state, distinct from lymphoid-primed multipotent progenitors, representing the earliest entry point into lymphoid commitment.

Suggested Citation

  • Serena Belluschi & Emily F. Calderbank & Valerio Ciaurro & Blanca Pijuan-Sala & Antonella Santoro & Nicole Mende & Evangelia Diamanti & Kendig Yen Chi Sham & Xiaonan Wang & Winnie W. Y. Lau & Wajid Ja, 2018. "Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06442-4
    DOI: 10.1038/s41467-018-06442-4
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    Cited by:

    1. Juan Jose Rodriguez-Sevilla & Vera Adema & Kelly S. Chien & Sanam Loghavi & Feiyang Ma & Hui Yang & Guillermo Montalban-Bravo & Xuelin Huang & Xavier Calvo & Joby Joseph & Kristy Bodden & Guillermo Ga, 2024. "The IL-1β inhibitor canakinumab in previously treated lower-risk myelodysplastic syndromes: a phase 2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Fernando Anjos-Afonso & Florian Buettner & Syed A. Mian & Hefin Rhys & Jimena Perez-Lloret & Manuel Garcia-Albornoz & Namrata Rastogi & Linda Ariza-McNaughton & Dominique Bonnet, 2022. "Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Kim Vanuytsel & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Zhe Wang & Wilfredo F. Garcia-Beltran & Vladimir Vrbanac & Dylan Parsons & Evan C. Lam & Taylor M. Matte & Todd W. Dowrey & Sara, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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