Figure 7. Circadian changes in the hematopoietic niche and progenitor trafficking are triggered by neutrophil clearance.

(A) Circadian oscillations in the number of neutrophils and CFU-C in the blood of WT mice. Arrowheads highlight the times of highest and lowest levels used for further analyses. Shaded areas represent periods of darkness.

(B–D) Daily fluctuations in the levels of hematopoietic progenitors in blood (black) and Abca1 transcripts in BM (dashed green) at ZT5 and ZT13 in control mice (B), or in mice in which neutrophils (C) or macrophages (D) were depleted. The lines represent the circadian variations of both parameters over a 29h period. Note that the point at ZT5 is repeated for clarity. n=8–14 mice for CFU-C; n=5 for Abca1 transcripts.

(E) Scheme summarizing the sequence of events identified in this study. CD62L^HI neutrophils are released into blood and age to become CD62L^LO CXCR4^HI. At specific times of the day, CD62L^LO neutrophils migrate back to the BM where they are phagocytosed by macrophages. Activation of LXR receptors is additionally required to induce reductions in the capacity of the hematopoietic niche to retain HPC, which are released into the bloodstream. All events indicated by arrows occur with circadian periodicity.

Data are shown as mean ± s.e.m. *P<0.05, **P<0.01, ***P<0.001.