title: High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice.
abstract: Blood formation by hematopoietic stem cells (HSCs) is regulated by a still incompletely defined network of general and HSC-specific regulators. In this study, we analyzed the role of G-protein coupled receptor 56 (Gpr56) as a candidate HSC regulator based on its differential expression in quiescent relative to proliferating HSCs and its common targeting by core HSC regulators. Detailed expression analysis revealed that Gpr56 is abundantly expressed by HSPCs during definitive hematopoiesis in the embryo and in the adult bone marrow, but its levels are reduced substantially as HSPCs differentiate. However, despite enriched expression in HSPCs, Gpr56-deficiency did not impair HSPC maintenance or function during steady-state or myeloablative stress-induced hematopoiesis. Gpr56-deficient HSCs also responded normally to physiological and pharmacological mobilization signals, despite the reported role of this GPCR as a regulator of cell adhesion and migration in neuronal cells. Moreover, Gpr56-deficient bone marrow engrafted with equivalent efficiency as wild-type HSCs in primary recipients; however, their reconstituting ability was reduced when subjected to serial transplantation. These data indicate that although GPR56 is abundantly and selectively expressed by primitive HSPCs, its high level expression is largely dispensable for steady-state and regenerative hematopoiesis.
authors.affiliation: Howard Hughes Medical Institute, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Tata Nageswara
authors.initials: TN
authors.lastname: Rao
authors.affiliation: Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Marks-Bluth
authors.affiliation: Howard Hughes Medical Institute, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Sullivan
authors.affiliation: Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Gupta
authors.affiliation: Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Vashe
authors.initials: V
authors.lastname: Chandrakanthan
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research University of Cambridge, Cambridge CB2 0XY, UK; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Fitch
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research University of Cambridge, Cambridge CB2 0XY, UK; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ottersbach
authors.affiliation: Howard Hughes Medical Institute, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Young C
authors.initials: YC
authors.lastname: Jang
authors.affiliation: Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, MA, USA.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Piao
authors.affiliation: Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.affiliation: Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Serwold
authors.affiliation: Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: John E
authors.initials: JE
authors.lastname: Pimanda
authors.affiliation: Howard Hughes Medical Institute, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Joslin Diabetes Center, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA. Electronic address: amy_wagers@harvard.edu.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; C524781:Adgrg1 protein, mouse
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