Hematopoietic-extrinsic cues dictate circadian redistribution of mature and immature hematopoietic cells in blood and spleen
- 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.
Author: | Miriam Stenzinger, Darja KarpovaORCiDGND, Christian Unterrainer, Sabine Harenkamp, Eliza WiercinskaORCiDGND, Keven Hoerster, Martina Pfeffer, Erik MarondeORCiDGND, Halvard-Björn BönigORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-532482 |
DOI: | https://doi.org/10.3390/cells8091033 |
ISSN: | 2073-4409 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31491915 |
Parent Title (German): | Cells |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2019/09/05 |
Date of first Publication: | 2019/09/05 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2020/05/11 |
Tag: | CXCL12; bmal1; circadian rhythm; clock genes; cortisol; hematopoiesis |
Volume: | 8 |
Issue: | 1033 |
Note: | 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. |
HeBIS-PPN: | 465006612 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |