Unexpected redundancy of Gpr56 and Gpr97 during hematopoietic cell development and differentiation

Antonio Maglitto, Samanta Mariani, E De Pater, Carmen Rodriguez Seoane, Chris Vink, X Piao, M L Lukke, Elaine Dzierzak

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Integrated molecular signals regulate cell fate decisions in the embryonic aortic endothelium to drive hematopoietic stem cell (HSC) generation during development. The G-protein coupled receptor 56 (Gpr56, also called Adgrg1) is the most highly- upregulated receptor gene in cells that take on hematopoietic fate and is expressed by adult bone marrow HSCs. Despite the requirement for Gpr56 in hematopoietic stem/progenitor cell (HS/PC) generation in zebrafish embryos and the highly- upregulated expression of GPR56 in treatment-resistant leukemic patients, its function in normal mammalian hematopoiesis remains unclear. Here we examine the role of Gpr56 in HS/PC development in Gpr56 conditional knockout (cKO) mouse embryos and Gpr knockout (KO) embryonic stem cell (ESC) hematopoietic differentiation cultures. Our results show a bias towards myeloid differentiation of Gpr56 cKO fetal liver HSCs and an increased definitive myeloid progenitor cell frequency in Gpr56KO ESC differentiation cultures. Surprisingly, we find that mouse Gpr97 can rescue Gpr56 morphant zebrafish hematopoietic generation, and that Gpr97 expression is upregulated in mouse Gpr56 deletion models. When both Gpr56 and Gpr97 are deleted in ESCs, no/few HPCs are generated upon ESC differentiation. Together, our results reveal novel and redundant functions for these two G-protein coupled receptors in normal mammalian hematopoietic cell development and differentiation.
Original languageEnglish
JournalBlood Advances
Publication statusPublished - 5 Feb 2021


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