Endogenous retinoid X receptor ligands in mouse hematopoietic cells

Science Signaling
Haixia NiuJohn S Welch

Abstract

The retinoid X receptor α (RXRA) has been implicated in diverse hematological processes. To identify natural ligands of RXRA that are present in hematopoietic cells, we adapted an upstream activation sequence-green fluorescent protein (UAS-GFP) reporter mouse to detect natural RXRA ligands in vivo. We observed reporter activity in diverse types of hematopoietic cells in vivo. Reporter activity increased during granulocyte colony-stimulating factor (G-CSF)-induced granulopoiesis and after phenylhydrazine (PHZ)-induced anemia, suggesting the presence of dynamically regulated natural RXRA ligands in hematopoietic cells. Mouse plasma activated Gal4-UAS reporter cells in vitro, and plasma from mice treated with G-CSF or PHZ recapitulated the patterns of reporter activation that we observed in vivo. Plasma from mice with dietary vitamin A deficiency only mildly reduced RXRA reporter activity, whereas plasma from mice on a fatty acid restriction diet reduced reporter activity, implicating fatty acids as plasma RXRA ligands. Through differential extraction coupled with mass spectrometry, we identified the long-chain fatty acid C24:5 as a natural RXRA ligand that was greatly increased in abundance in response to hematopoietic stress. To...Continue Reading

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Citations

Dec 7, 2019·Cancers·Orsola di Martino, John S Welch
Jul 11, 2018·International Journal of Molecular Sciences·Michiyasu IshizawaMakoto Makishima
Nov 27, 2020·Haematologica·Orsola Di MartinoJohn S Welch
Feb 5, 2021·Haematologica·Tomohide SuzukiYoshio Katayama
Jan 27, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Baixue LiJames L Boyer
Mar 3, 2021·Blood·Marie-Claude GeoffroyHugues de Thé
Aug 8, 2021·International Journal of Molecular Sciences·Ana ParedesMercedes Ricote

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