TY - JOUR A1 - Stenzinger, Miriam A1 - Karpova, Darja A1 - Unterrainer, Christian A1 - Harenkamp, Sabine A1 - Wiercinska, Eliza A1 - Hoerster, Keven A1 - Pfeffer, Martina A1 - Maronde, Erik A1 - Bönig, Halvard-Björn T1 - Hematopoietic-extrinsic cues dictate circadian redistribution of mature and immature hematopoietic cells in blood and spleen T2 - Cells N2 - Circadian oscillations in circulating leukocyte subsets including immature hematopoietic cells have been appreciated; the origin and nature of these alterations remain elusive. Our analysis of wild-type C57BL/6 mice under constant darkness confirmed circadian fluctuations of circulating leukocytes and clonogenic cells in blood and spleen but not bone marrow. Clock gene deficient Bmal1-/- mice lacked this regulation. Cell cycle analyses in the different hematopoietic compartments excluded circadian changes in total cell numbers, rather favoring shifting hematopoietic cell redistribution as the underlying mechanism. Transplant chimeras demonstrate that circadian rhythms within the stroma mediate the oscillations independently of hematopoietic-intrinsic cues. We provide evidence of circadian CXCL12 regulation via clock genes in vitro and were able to confirm CXCL12 oscillation in bone marrow and blood in vivo. Our studies further implicate cortisol as the conveyor of circadian input to bone marrow stroma and mediator of the circadian leukocyte oscillation. In summary, we establish hematopoietic-extrinsic cues as causal for circadian redistribution of circulating mature/immature blood cells. KW - hematopoiesis KW - circadian rhythm KW - clock genes KW - bmal1 KW - CXCL12 KW - cortisol Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53248 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-532482 SN - 2073-4409 N1 - This is an Open Access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. VL - 8 IS - 1033 PB - MDPI CY - Basel ER -