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Haematopoietic stem cell release is regulated by circadian oscillations

Author

Listed:
  • Simón Méndez-Ferrer

    (Mount Sinai School of Medicine, New York, New York 10029, USA)

  • Daniel Lucas

    (Mount Sinai School of Medicine, New York, New York 10029, USA)

  • Michela Battista

    (Mount Sinai School of Medicine, New York, New York 10029, USA)

  • Paul S. Frenette

    (Mount Sinai School of Medicine, New York, New York 10029, USA
    Black Family Stem Cell Institute, New York, New York 10029, USA
    Immunology Institute, New York, New York 10029, USA)

Abstract

Haematopoietic stem cells (HSCs) circulate in the bloodstream under steady-state conditions, but the mechanisms controlling their physiological trafficking are unknown. Here we show that circulating HSCs and their progenitors exhibit robust circadian fluctuations, peaking 5 h after the initiation of light and reaching a nadir 5 h after darkness. Circadian oscillations are markedly altered when mice are subjected to continuous light or to a ‘jet lag’ (defined as a shift of 12 h). Circulating HSCs and their progenitors fluctuate in antiphase with the expression of the chemokine CXCL12 in the bone marrow microenvironment. The cyclical release of HSCs and expression of Cxcl12 are regulated by core genes of the molecular clock through circadian noradrenaline secretion by the sympathetic nervous system. These adrenergic signals are locally delivered by nerves in the bone marrow, transmitted to stromal cells by the β3-adrenergic receptor, leading to a decreased nuclear content of Sp1 transcription factor and the rapid downregulation of Cxcl12. These data indicate that a circadian, neurally driven release of HSC during the animal’s resting period may promote the regeneration of the stem cell niche and possibly other tissues.

Suggested Citation

  • Simón Méndez-Ferrer & Daniel Lucas & Michela Battista & Paul S. Frenette, 2008. "Haematopoietic stem cell release is regulated by circadian oscillations," Nature, Nature, vol. 452(7186), pages 442-447, March.
    • Handle: RePEc:nat:nature:v:452:y:2008:i:7186:d:10.1038_nature06685
    DOI: 10.1038/nature06685
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    Cited by:

    1. Claire Fielding & Andrés García-García & Claudia Korn & Stephen Gadomski & Zijian Fang & Juan L. Reguera & José A. Pérez-Simón & Berthold Göttgens & Simón Méndez-Ferrer, 2022. "Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Shen Y. Heazlewood & Tanveer Ahmad & Benjamin Cao & Huimin Cao & Melanie Domingues & Xuan Sun & Chad K. Heazlewood & Songhui Li & Brenda Williams & Madeline Fulton & Jacinta F. White & Tom Nebl & Chri, 2023. "High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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