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Cell Rep. 2016 Oct 4;17(2):458-468. doi: 10.1016/j.celrep.2016.09.012.

Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production.

Author information

1
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
2
Boston Children's Hospital, Boston, MA 02115, USA.
3
Department of Biological Sciences, California State University, Chico, Chico, CA 95929, USA.
4
Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
5
Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
6
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: tnorth@bidmc.harvard.edu.

Abstract

Vitamin D insufficiency is a worldwide epidemic affecting billions of individuals, including pregnant women and children. Despite its high incidence, the impact of active vitamin D3 (1,25(OH)D3) on embryonic development beyond osteo-regulation remains largely undefined. Here, we demonstrate that 1,25(OH)D3 availability modulates zebrafish hematopoietic stem and progenitor cell (HSPC) production. Loss of Cyp27b1-mediated biosynthesis or vitamin D receptor (VDR) function by gene knockdown resulted in significantly reduced runx1 expression and Flk1+cMyb+ HSPC numbers. Selective modulation in vivo and in vitro in zebrafish indicated that vitamin D3 acts directly on HSPCs, independent of calcium regulation, to increase proliferation. Notably, ex vivo treatment of human HSPCs with 1,25(OH)D3 also enhanced hematopoietic colony numbers, illustrating conservation across species. Finally, gene expression and epistasis analysis indicated that CXCL8(IL-8) was a functional target of vitamin D3-mediated HSPC regulation. Together, these findings highlight the relevance of developmental 1,25(OH)D3 availability for definitive hematopoiesis and suggest potential therapeutic utility in HSPC expansion.

KEYWORDS:

1,25(OH)D3; CFU-C; cxcl8; hUCB; hematopoietic stem cell (HSC); vitamin D; zebrafish

PMID:
27705794
PMCID:
PMC5338633
DOI:
10.1016/j.celrep.2016.09.012
[Indexed for MEDLINE]
Free PMC Article

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