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Clonal dynamics of native haematopoiesis

Author

Listed:
  • Jianlong Sun

    (Stem Cell Program, Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute)

  • Azucena Ramos

    (Stem Cell Program, Children’s Hospital)

  • Brad Chapman

    (Harvard School of Public Health)

  • Jonathan B. Johnnidis

    (University of Pennsylvania)

  • Linda Le

    (Stem Cell Program, Children’s Hospital)

  • Yu-Jui Ho

    (Watson School of Biological Sciences, Cold Spring Harbor Laboratory)

  • Allon Klein

    (Harvard Medical School)

  • Oliver Hofmann

    (Harvard School of Public Health)

  • Fernando D. Camargo

    (Stem Cell Program, Children’s Hospital
    Harvard University
    Harvard Stem Cell Institute)

Abstract

It is currently thought that life-long blood cell production is driven by the action of a small number of multipotent haematopoietic stem cells. Evidence supporting this view has been largely acquired through the use of functional assays involving transplantation. However, whether these mechanisms also govern native non-transplant haematopoiesis is entirely unclear. Here we have established a novel experimental model in mice where cells can be uniquely and genetically labelled in situ to address this question. Using this approach, we have performed longitudinal analyses of clonal dynamics in adult mice that reveal unprecedented features of native haematopoiesis. In contrast to what occurs following transplantation, steady-state blood production is maintained by the successive recruitment of thousands of clones, each with a minimal contribution to mature progeny. Our results demonstrate that a large number of long-lived progenitors, rather than classically defined haematopoietic stem cells, are the main drivers of steady-state haematopoiesis during most of adulthood. Our results also have implications for understanding the cellular origin of haematopoietic disease.

Suggested Citation

  • Jianlong Sun & Azucena Ramos & Brad Chapman & Jonathan B. Johnnidis & Linda Le & Yu-Jui Ho & Allon Klein & Oliver Hofmann & Fernando D. Camargo, 2014. "Clonal dynamics of native haematopoiesis," Nature, Nature, vol. 514(7522), pages 322-327, October.
  • Handle: RePEc:nat:nature:v:514:y:2014:i:7522:d:10.1038_nature13824
    DOI: 10.1038/nature13824
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    Cited by:

    1. Yu-Jung Tseng & Yuki Kageyama & Rebecca L. Murdaugh & Ayumi Kitano & Jong Hwan Kim & Kevin A. Hoegenauer & Jonathan Tiessen & Mackenzie H. Smith & Hidetaka Uryu & Koichi Takahashi & James F. Martin & , 2024. "Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Trent D. Hall & Hyunjin Kim & Mahmoud Dabbah & Jacquelyn A. Myers & Jeremy Chase Crawford & Antonio Morales-Hernandez & Claire E. Caprio & Pramika Sriram & Emilia Kooienga & Marta Derecka & Esther A. , 2022. "Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. 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.
    4. 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.
    5. C. Biben & T. S. Weber & K. S. Potts & J. Choi & D. C. Miles & A. Carmagnac & T. Sargeant & C. A. Graaf & K. A. Fennell & A. Farley & O. J. Stonehouse & M. A. Dawson & D. J. Hilton & S. H. Naik & S. T, 2023. "In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Adrienne Anginot & Julie Nguyen & Zeina Abou Nader & Vincent Rondeau & Amélie Bonaud & Maria Kalogeraki & Antoine Boutin & Julia P. Lemos & Valeria Bisio & Joyce Koenen & Lea Hanna Doumit Sakr & Amand, 2023. "WHIM Syndrome-linked CXCR4 mutations drive osteoporosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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