1. Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance
- Author
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Biana Bernshtein, Irit Sagi, Orit Kollet, Andrzej Ciechanowicz, John E. Dick, Eman Khatib-Massalha, Sylwia Rzeszotek, Eugenia Flores-Figueroa, Shiri Gur-Cohen, Francesca Avemaria, Tsvee Lapidot, Mayla Bertagna, Aya Ludin-Tal, Mohana Devi Subramaniam, Nathali Kaushansky, Regina P. Markus, Hassan Massalha, Tevie Mehlman, Mariusz Z. Ratajczak, Karin Golan, Simón Méndez-Ferrer, Anju Kumari, Tomer Itkin, Andrés García-García, Zulma S. Ferreira, Hui Cheng, Tomasz Janus, Stephanie Z. Xie, Ekaterina Petrovich-Kopitman, Alexander Brandis, Tao Cheng, Suditi Bhattacharya, Ferreira, Zulma S [0000-0001-6571-837X], Rzeszotek, Sylwia [0000-0002-2157-0315], Xie, Stephanie [0000-0002-0284-494X], Flores-Figueroa, Eugenia [0000-0002-7453-1125], Gur-Cohen, Shiri [0000-0002-6372-2284], Ciechanowicz, Andrzej K [0000-0003-0052-136X], Ratajczak, Mariusz Z [0000-0002-0071-0198], Méndez-Ferrer, Simón [0000-0002-9805-9988], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,bone marrow ,light and darkness ,Light ,stem cell repopulation potential ,hematopoietic stem and progenitor cells ,TNF ,Vascular permeability ,melatonin ,Biology ,norepinephrine ,Epigenesis, Genetic ,Melatonin ,Blood cell ,03 medical and health sciences ,Mice ,maintenance and retention ,Genetics ,medicine ,Animals ,Progenitor cell ,vascular permeability ,Cells, Cultured ,Hematopoietic stem cell differentiation ,differentiation and egress ,Cell Differentiation ,Cell Biology ,Darkness ,Hematopoietic Stem Cells ,Cell biology ,Mice, Inbred C57BL ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Molecular Medicine ,Bone marrow ,Stem cell ,medicine.drug ,Transcription Factors - 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.
- Published
- 2017