Haematopoietic stem cell release is regulated by circadian oscillations

Simón Méndez-Ferrer, Daniel Lucas, Michela Battista, Paul S. Frenette

Research output: Contribution to journalArticle

693 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)442-447
Number of pages6
JournalNature
Volume452
Issue number7186
DOIs
StatePublished - Mar 27 2008
Externally publishedYes

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Hematopoietic Stem Cells
Bone Marrow
Sp1 Transcription Factor
Stem Cell Niche
Chemokine CXCL12
Light
Circadian Clocks
Darkness
Sympathetic Nervous System
Stromal Cells
Adrenergic Agents
Adrenergic Receptors
Regeneration
Norepinephrine
Down-Regulation
Genes

ASJC Scopus subject areas

  • General

Cite this

Haematopoietic stem cell release is regulated by circadian oscillations. / Méndez-Ferrer, Simón; Lucas, Daniel; Battista, Michela; Frenette, Paul S.

In: Nature, Vol. 452, No. 7186, 27.03.2008, p. 442-447.

Research output: Contribution to journalArticle

Méndez-Ferrer, S, Lucas, D, Battista, M & Frenette, PS 2008, 'Haematopoietic stem cell release is regulated by circadian oscillations', Nature, vol. 452, no. 7186, pp. 442-447. https://doi.org/10.1038/nature06685
Méndez-Ferrer, Simón ; Lucas, Daniel ; Battista, Michela ; Frenette, Paul S. / Haematopoietic stem cell release is regulated by circadian oscillations. In: Nature. 2008 ; Vol. 452, No. 7186. pp. 442-447.
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