Pharmacological activation of LPA receptors regulates erythro‐megakaryocytic differentiation in myeloid lineage

Myeloid cell differentiation is one of the crucial process of hematopoiesis. It has been revealed that lysophosphatidic acid (LPA), through activating G‐protein‐coupled receptors of LPA 1–6 , may contribute to the regulation of this process. However, the underlie mechanisms in vivo remains unclear. Here, we aim to investigate the effects of LPA and its corresponding receptors, LPA 2 and LPA 3 , during erythropoiesis/megakaryopoiesis. Two chemical drugs, LPA 2 agonist GRI977143 and LPA 3 agonist 1‐oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate (OMPT) were injected in BALB/ c mice. Blood samples were collected and analyzed to determine the quantity of differentiation‐stage‐specific erythro‐megakaryocytic progenitors in spleen/bone marrow and terminally differentiated cells in circulatory blood, respectively. Our results revealed that the activation of LPA 2 inhibit erythro‐megakaryocytic differentiation, whereas activation of LPA 3 may promote erythroid development and decrease megakaryocyte generation in vivo . These result implied that LPA 2 may dominate and inhibit the erythro‐megakaryocytic differentiation in the early stage of myeloid lineage. In contrast, LPA 3 mainly regulates and promotes erythroid differentiation except for megakaryocyte. Taken together, our findings showing a remarkable difference between LPA receptor activation on regulating hematopoiesis in vivo. Moreover, the detailed impacts of LPA 2/3 on different stages of myeloid stem cells during erythropoiesis/megakaryopoiesis will be elucidated in the future.