Cell Stem Cell
Volume 23, Issue 4, 4 October 2018, Pages 572-585.e7
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Article
Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance

https://doi.org/10.1016/j.stem.2018.08.002Get rights and content
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Highlights

  • Light and dark onset induce BM NE and TNF bursts, which transiently upregulate ROS in HSPCs

  • NE and TNF ROS bursts induce functionally distinct 11 a.m. and 11 p.m. HSPC peaks

  • 11 a.m. peaks of NE induce vascular permeability and HSPC differentiation and egress

  • 11 p.m. peaks of melatonin increase CD150+ expression and HSC retention and self-renewal

Summary

Hematopoietic stem and progenitor cells (HSPCs) tightly couple maintenance of the bone marrow (BM) reservoir, including undifferentiated long-term repopulating hematopoietic stem cells (LT-HSCs), with intensive daily production of mature leukocytes and blood replenishment. We found two daily peaks of BM HSPC activity that are initiated by onset of light and darkness providing this coupling. Both peaks follow transient elevation of BM norepinephrine and TNF secretion, which temporarily increase HSPC reactive oxygen species (ROS) levels. Light-induced norepinephrine and TNF secretion augments HSPC differentiation and increases vascular permeability to replenish the blood. In contrast, darkness-induced TNF increases melatonin secretion to drive renewal of HSPCs and LT-HSC potential through modulating surface CD150 and c-Kit expression, increasing COX-2/αSMA+ macrophages, diminishing vascular permeability, and reducing HSPC ROS levels. These findings reveal that light- and darkness-induced daily bursts of norepinephrine, TNF, and melatonin within the BM are essential for synchronized mature blood cell production and HSPC pool repopulation.

Keywords

hematopoietic stem and progenitor cells
light and darkness
TNF
melatonin
norepinephrine
bone marrow
differentiation and egress
maintenance and retention
vascular permeability
stem cell repopulation potential

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