Endogenous retinoid X receptor ligands in mouse hematopoietic cells

Haixia Niu, Hideji Fujiwara, Orsola Di Martino, Gayla Hadwiger, Thomas E. Frederick, Maria P. Menéndez-Gutiérrez, Mercedes Ricote, Gregory R. Bowman, John S. Welch

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The retinoid X receptor a (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 treatedwith G-CSF or PHZ recapitulated the patterns of reporter activation thatwe observed in vivo. Plasma from mice with dietary vitamin Adeficiency onlymildly reduced RXRAreporter activity,whereas plasma frommice on a fatty acid restriction diet reduced reporter activity, implicating fatty acids as plasma RXRA ligands. Through differential extraction coupled withmass 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.

Original languageEnglish
Article numbereaan1011
JournalScience signaling
Volume10
Issue number503
DOIs
StatePublished - Oct 31 2017

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