ZFIN ID: ZDB-PUB-161007-11
Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production
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.
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.
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.