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Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells

Author

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  • Amit Grover

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Institute for Stem Cell Research, University of Edinburgh)

  • Alejandra Sanjuan-Pla

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Institute for Stem Cell Research, University of Edinburgh)

  • Supat Thongjuea

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Joana Carrelha

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford)

  • Alice Giustacchini

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford)

  • Adriana Gambardella

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Institute for Stem Cell Research, University of Edinburgh
    EMBL Mouse Biology Program)

  • Iain Macaulay

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford)

  • Elena Mancini

    (EMBL Mouse Biology Program)

  • Tiago C. Luis

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford)

  • Adam Mead

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford)

  • Sten Eirik W. Jacobsen

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Haemopoietic Stem Cell Laboratory, Weatherall Institute for Molecular Medicine, University of Oxford)

  • Claus Nerlov

    (MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Institute for Stem Cell Research, University of Edinburgh
    EMBL Mouse Biology Program)

Abstract

Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Here, by analysing HSC transcriptomes and HSC function at the single-cell level, we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets. Depletion of HSC platelet programming through loss of the FOG-1 transcription factor is accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis.

Suggested Citation

  • Amit Grover & Alejandra Sanjuan-Pla & Supat Thongjuea & Joana Carrelha & Alice Giustacchini & Adriana Gambardella & Iain Macaulay & Elena Mancini & Tiago C. Luis & Adam Mead & Sten Eirik W. Jacobsen &, 2016. "Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11075
    DOI: 10.1038/ncomms11075
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    Cited by:

    1. Harold K. Elias & Sneha Mitra & Marina B. Silva & Adhithi Rajagopalan & Brianna Gipson & Nicole Lee & Anastasia I. Kousa & Mohamed A. E. Ali & Simon Grassmann & Rhoshini Raghuraman & Xiaoqun C. Zhang , 2025. "Kitlo hematopoietic stem cells exhibit distinct lymphoid-primed chromatin landscapes that enhance thymic reconstitution," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    2. Mina N. F. Morcos & Congxin Li & Clara M. Munz & Alessandro Greco & Nicole Dressel & Susanne Reinhardt & Katrin Sameith & Andreas Dahl & Nils B. Becker & Axel Roers & Thomas Höfer & Alexander Gerbaule, 2022. "Fate mapping of hematopoietic stem cells reveals two pathways of native thrombopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Tsu-Yi Su & Julia Hauenstein & Ece Somuncular & Özge Dumral & Elory Leonard & Charlotte Gustafsson & Efthymios Tzortzis & Aurora Forlani & Anne-Sofie Johansson & Hong Qian & Robert Månsson & Sidinh Lu, 2024. "Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Natasha M. Nesbitt & Gian Luca Araldi & Lisa Pennacchia & Natalia Marchenko & Zahra Assar & Kendall M. Muzzarelli & Rahul Raghavan Thekke Veedu & Brian Medel-Lacruz & Eunjeong Lee & Elan Z. Eisenmesse, 2025. "Small molecule BLVRB redox inhibitor promotes megakaryocytopoiesis and stress thrombopoiesis in vivo," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    5. Steicy Sobrino & Laure Joseph & Elisa Magrin & Anne Chalumeau & Nicolas Hebert & Alice Corsia & Adeline Denis & Cécile Roudaut & Clotilde Aussel & Olivia Leblanc & Mégane Brusson & Tristan Felix & Jea, 2025. "Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    6. Jos Urbanus & Jason Cosgrove & Joost B. Beltman & Yuval Elhanati & Rafael A. Moral & Cecile Conrad & Jeroen W. Heijst & Emilie Tubeuf & Arno Velds & Lianne Kok & Candice Merle & Jens P. Magnusson & Lé, 2023. "DRAG in situ barcoding reveals an increased number of HSPCs contributing to myelopoiesis with age," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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