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

Karin Golan, Anju Kumari, Orit Kollet, Eman Khatib-Massalha, Mohana Devi Subramaniam, Zulma S. Ferreira, Francesca Avemaria, Sylwia Rzeszotek, Andres Garcia-Garcia, Stephanie Xie, Eugenia Flores-Figueroa, Shiri Gur-Cohen, Tomer Itkin, Aya Ludin-Tal, Hassan Massalha, Biana Bernshtein, Andrzej K. Ciechanowicz, Alexander Brandis, Tevie Mehlman, Suditi BhattacharyaMayla Bertagna, Hui Cheng, Ekaterina Petrovich-Kopitman, Tomasz Janus, Nathali Kaushansky, Tao Cheng, Irit Sagi, Mariusz Z. Ratajczak, Simon Mendez-Ferrer, John E. Dick, Regina P. Markus, Tsvee Lapidot

Research output: Contribution to journalArticlepeer-review


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. Golan et al. report that daily onsets of light and dark induce NE and TNF bursts that induce two different peaks of BM HSPC activity. Light-induced NE promotes HSPC differentiation and egress, replenishing mature blood cells. Dark-induced TNF promotes melatonin-dependent renewal of CD150 + HSCs and their long-term repopulation potential.

Original languageEnglish
Pages (from-to)572-585
Number of pages14
JournalCell Stem Cell
Issue number4
Early online date21 Aug 2018
StatePublished - 4 Oct 2018

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology


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