Antagonizing Retinoic Acid Receptors Increases Myeloid Cell Production by Cultured Human Hematopoietic Stem Cells

• DOI: 10.1007/s00005-016-0411-0
• Publication Date: 2016-07-13T09:03:35Z
• Authors: Geoffrey Brown; Aleksandra Marchw...; Alan Cunningham; Kai-Michael Toellner; Ewa Marcinkowska
• Keywords: Hematopoietic stem cell

Activities of the retinoic acid receptor (RAR)α and RARγ are important to hematopoiesis. Here, we have investigated effects selective agonists antagonists on primitive human hematopoietic cell lines KG1 NB-4 purified normal stem cells (HSCs). Agonizing RARα (by AGN195183) was effective in driving neutrophil differentiation this agonist synergized with a low amount (10 nM) 1α,25-dihydroxyvitamin D3 drive monocyte cells. Treatment cultures HSCs (supplemented factor ± interleukin 3) an antagonist all RARs (AGN194310) or (AGN196996) prolonged lifespan cultures, up 55 days, increased production neutrophils monocytes. Slowing down not observed, instead, progenitor had expanded number. Antagonism AGN205728) did affect HSCs. Studies CV-1 LNCaP transfected RAR expression vectors reporter vector revealed that RARβ activated by sub-nM all-trans (EC50-0.3 nM): ~50-fold more is required for activation (EC50-16 nM). These findings further support notion balance activity expansion differentiation.