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- Title
Endogenous retinoid X receptor ligands in mouse hematopoietic cells.
- Authors
Niu, Haixia; Fujiwara, Hideji; di Martino, Orsola; Hadwiger, Gayla; Frederick, Thomas E.; Menéndez-Gutiérrez, María P.; Ricote, Mercedes; Bowman, Gregory R.; Welch, John S.
- 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 treated with G-CSF or PHZ recapitulated the patterns of reporter activation that we observed in vivo. Plasma from mice with dietary vitamin Adeficiency onlymildly 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.
- Subjects
RETINOID X receptors; LIGANDS (Biochemistry); HEMATOPOIETIC growth factors; PROTEINS; LABORATORY mice
- Publication
Science Signaling, 2017, Vol 10, Issue 503, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aan1011