PUBLICATION
The Orphan G-Protein Coupled Receptor 182 Is a Negative Regulator of Definitive Hematopoiesis through Leukotriene B4 Signaling
- Authors
- Kwon, H.B., Mackie, D.I., Bonnavion, R., Mercier, A.L., Helker, C.S.M., Son, T., Guenter, S., Serafin, D.S., Kim, K.W., Offermanns, S., Caron, K.M., Stainier, D.Y.R.
- ID
- ZDB-PUB-200825-9
- Date
- 2020
- Source
- ACS pharmacology & translational science 3: 676-689 (Journal)
- Registered Authors
- Helker, Christian, Stainier, Didier
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 32832870 Full text @ ACS Pharmacol Transl Sci
Citation
Kwon, H.B., Mackie, D.I., Bonnavion, R., Mercier, A.L., Helker, C.S.M., Son, T., Guenter, S., Serafin, D.S., Kim, K.W., Offermanns, S., Caron, K.M., Stainier, D.Y.R. (2020) The Orphan G-Protein Coupled Receptor 182 Is a Negative Regulator of Definitive Hematopoiesis through Leukotriene B4 Signaling. ACS pharmacology & translational science. 3:676-689.
Abstract
The G protein-coupled receptor 182 (GPR182) is an orphan GPCR, the expression of which is enriched in embryonic endothelial cells (ECs). However, the physiological role and molecular mechanism of action of GPR182 are unknown. Here, we show that GPR182 negatively regulates definitive hematopoiesis in zebrafish and mice. In zebrafish, gpr182 expression is enriched in the hemogenic endothelium (HE), and gpr182-/- display an increased expression of HE and hematopoietic stem cell (HSC) marker genes. Notably, we find an increased number of myeloid cells in gpr182-/- compared to wild-type. Further, by time-lapse imaging of zebrafish embryos during the endothelial-to-hematopoietic transition, we find that HE/HSC cell numbers are increased in gpr182-/- compared to wild-type. GPR182-/- mice also exhibit an increased number of myeloid cells compared to wild-type, indicating a conserved role for GPR182 in myelopoiesis. Using cell-based small molecule screening and transcriptomic analyses, we further find that GPR182 regulates the leukotriene B4 (LTB4) biosynthesis pathway. Taken together, these data indicate that GPR182 is a negative regulator of definitive hematopoiesis in zebrafish and mice, and provide further evidence for LTB4 signaling in HSC biology.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping