title: The lysophosphatidic acid receptor LPA4 regulates hematopoiesis-supporting activity of bone marrow stromal cells.
abstract: Lysophosphatidic acid (LPA) is a pleiotropic lipid mediator that acts through G protein-coupled receptors (LPA1-6). Although several biological roles of LPA4 are becoming apparent, its role in hematopoiesis has remained unknown. Here, we show a novel regulatory role for LPA4 in hematopoiesis. Lpar4 mRNA was predominantly expressed in mouse bone marrow (BM) PDGFRα(+) stromal cells, known as the components of the hematopoietic stem/progenitor cell (HSPC) niche. Compared with wild-type mice, LPA4-deficient mice had reduced HSPC numbers in the BM and spleen and were hypersusceptible to myelosuppression, most likely due to impairments in HSPC recovery and stem cell factor production in the BM. Analysis of reciprocal BM chimeras (LPA4-deficient BM into wild-type recipients and vice versa) indicated that stromal cells likely account for these phenotypes. Consistently, LPA4-deficient BM stromal cells showed downregulated mRNA expression of stem cell factor and tenascin-c in vitro. Taken together, these results suggest a critical and novel role for the LPA/LPA4 axis in regulating BM stromal cells.
authors.affiliation: Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Igarashi
authors.affiliation: Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akahoshi
authors.affiliation: Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Takayo
authors.initials: T
authors.lastname: Ohto-Nakanishi
authors.affiliation: Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yasuda
authors.affiliation: Department of Immunology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000378:metabolism; D002452:Cell Count; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000235:genetics / Q000378:metabolism*; D013154:Spleen; D019089:Stem Cell Factor / Q000096:biosynthesis
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; C523574:Lpar4 protein, mouse; D049368:Receptors, Lysophosphatidic Acid; D011983:Receptors, Purinergic; D019089:Stem Cell Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D005472:Fluorouracil