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Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance.

Accepted version
Peer-reviewed

Type

Article

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Authors

Golan, Karin 
Kumari, Anju 
Kollet, Orit 
Khatib-Massalha, Eman 
Subramaniam, Mohana Devi 

Abstract

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.

Description

Keywords

TNF, bone marrow, differentiation and egress, hematopoietic stem and progenitor cells, light and darkness, maintenance and retention, melatonin, norepinephrine, stem cell repopulation potential, vascular permeability, Animals, Cell Differentiation, Cells, Cultured, Darkness, Epigenesis, Genetic, Hematopoietic Stem Cells, Light, Mice, Mice, Inbred C57BL, Transcription Factors

Journal Title

Cell Stem Cell

Conference Name

Journal ISSN

1934-5909
1875-9777

Volume Title

23

Publisher

Elsevier BV
Sponsorship
European Research Council (648765)
NHS Blood and Transplant (NHSBT)
Medical Research Council (MC_PC_12009)