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High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice.

TitleHigh-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice.
Publication TypeJournal Article
Year of Publication2015
AuthorsRao TNageswara, Marks-Bluth J, Sullivan J, Gupta MK, Chandrakanthan V, Fitch SR, Ottersbach K, Jang YC, Piao X, Kulkarni RN, Serwold T, Pimanda JE, Wagers AJ
JournalStem Cell Res
Volume14
Issue3
Pagination307-22
Date Published2015 May
ISSN1876-7753
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.

DOI10.1016/j.scr.2015.02.001
Alternate JournalStem Cell Res
PubMed ID25840412
PubMed Central IDPMC4439311
Grant ListDP2 OD004345 / OD / NIH HHS / United States
P30 DK036836 / DK / NIDDK NIH HHS / United States
R01 DK067536 / DK / NIDDK NIH HHS / United States
R01 DK103215 / DK / NIDDK NIH HHS / United States
R01 HL088582 / HL / NHLBI NIH HHS / United States
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