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oai:repisalud.isciii.es:20.500.12105/151402024-09-27T10:03:19Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Niu, Haixia author Fujiwara, Hideji author di Martino, Orsola author Hadwiger, Gayla author Frederick, Thomas E author Menéndez-Gutiérrez, María P author Ricote, Mercedes author Bowman, Gregory R author Welch, John S author 2017-10-31 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. Together, these data suggest that natural RXRA ligands are present and dynamically increased in abundance in mouse hematopoietic cells in vivo. Sci Signal . 2017 Oct 31;10(503):eaan1011. doi: 10.1126/scisignal.aan1011. 10.1126/scisignal.aan1011 1937-9145 Science signaling 29089448 http://hdl.handle.net/20.500.12105/15140 Endogenous retinoid X receptor ligands in mouse hematopoietic cells.