PUBLICATION

Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production

Authors
Cortes, M., Chen, M.J., Stachura, D.L., Liu, S.Y., Kwan, W., Wright, F., Vo, L.T., Theodore, L.N., Esain, V., Frost, I.M., Schlaeger, T.M., Goessling, W., Daley, G.Q., North, T.E.
ID
ZDB-PUB-161007-11
Date
2016
Source
Cell Reports   17: 458-468 (Journal)
Registered Authors
Daley, Rachael, Goessling, Wolfram, North, Trista, Schlaeger, Thorsten
Keywords
1,25(OH)D3, CFU-C, cxcl8, hUCB, hematopoietic stem cell (HSC), vitamin D, zebrafish
MeSH Terms
  • Animals
  • Biological Availability
  • Calcium Signaling/genetics
  • Core Binding Factor Alpha 2 Subunit/genetics
  • Cytochrome P-450 Enzyme System/genetics*
  • Embryonic Development/genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Hematopoiesis/genetics
  • Hematopoietic Stem Cells/metabolism*
  • Humans
  • Interleukin-8/genetics*
  • Interleukin-8/metabolism
  • Pregnancy
  • Receptors, Calcitriol/genetics*
  • Vascular Endothelial Growth Factor Receptor-2/genetics
  • Vitamin D/genetics*
  • Vitamin D/metabolism
  • Vitamin D Deficiency/genetics
  • Vitamin D Deficiency/metabolism
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
PubMed
27705794 Full text @ Cell Rep.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes