Significance Small-molecule enhancers of hematopoietic stem cell transplant could improve the safety of this treatment and expand the pool of eligible patients. We previously showed that the lipid 11,12-epoxyeicosatrienoic acid (EET) enhanced transplant in zebrafish and mice. We use a bioinformatic approach to identify candidate EET receptors and demonstrate that EET activates GPR132. We find that this receptor is important in zebrafish and mouse hematopoiesis, and we further show that GPR132 has responsiveness to additional oxygenated polyunsaturated fatty acids such as EET. Thus, GPR132 receives lipid-derived signals to regulate hematopoiesis and is a therapeutic target for enhancing HSC transplant.