Browsing by Subject "Proton-sensing G protein-coupled receptors"

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    Whole body deletion of Gpr68 does not change hematopoietic stem cell function
    (Elsevier, 2020-06-20) He, Xiaofei; Hawkins, Caleb; Lawley, Lauren; Freeman, Kennedy; Phan, Tra Mi; Zhang, Jiajia; Xu, Yan; Fang, Jing; Obstetrics and Gynecology, School of Medicine
    G protein-coupled receptor 68 (GPR68) responds to extracellular protons, thus called the proton-sensing G protein-coupled receptor (GPCR), leading to activation of the phospholipase C-β (PLCβ)/calcium (Ca2+) pathway or the adenylyl cyclase (AC)/cyclic AMP (cAMP) pathway. We recently found that whole body deletion of Gpr68 (Gpr68-/- mice) reduced the number of B lymphocytes with age and during hematopoietic regeneration, such as in response to fluorouracil (5-FU) administration. This prompted us to characterize the hematopoietic stem cell (HSC) phenotype in Gpr68-/- mice. Despite high level of Gpr68 protein expression on HSC in bone marrow (BM), the pool size of HSC was unaltered in Gpr68-/- mice either under steady state or upon stress, including aging and 5-FU treatment. HSC from Gpr68-/- mice exhibited comparable cellular features, such as cell cycle quiescence and cell survival. HSC from Gpr68-/- mice also exhibited comparable competitiveness after serial transplantation. Surprisingly, cytosolic Ca2+ accumulation was increased in HSC from Gpr68-/- mice. In contrast, cAMP levels were reduced in hematopoietic stem and progenitor cells (HSPC) from Gpr68-/- mice. Intriguingly, we found high level of Gpr68 protein expression on non-hematopoietic cells in BM, especially endothelial cells that function as HSC niche. In addition, expression of other proton-sensing GPCR was upregulated in HSPC from Gpr68-/- mice. Our studies suggest that Gpr68-/- mice display insignificant phenotype on HSC biology, possibly due to the function of Gpr68 in non-hematopoietic cells and/or the compensatory effects from other proton-sensing GPCR.