Activation of Lysophosphatidic Acid Receptor 3 Inhibits Megakaryopoiesis in Human Hematopoietic Stem Cells and Zebrafish
| Autor: | Hsinyu Lee, Wei-Chun Weng, Chao-Ling Yao, Chang-Jen Huang, Bei-En Chang, Meng Wei Li, Ya Hsuan Ho, Kuan-Hung Lin, Ya-Chi Chang, Yu-Nung Lin |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cellular differentiation Stem cell factor Thrombopoiesis 03 medical and health sciences 0302 clinical medicine Animals Humans Receptors Lysophosphatidic Acid Zebrafish Megakaryopoiesis LPAR3 biology Cell Biology Hematology Zebrafish Proteins Hematopoietic Stem Cells biology.organism_classification Cell biology 030104 developmental biology 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Lysophosphatidic Acid Receptor 3 Stem cell Megakaryocytes Developmental Biology |
| Zdroj: | Stem Cells and Development. 27:216-224 |
| ISSN: | 1557-8534 1547-3287 |
| DOI: | 10.1089/scd.2017.0190 |
| Popis: | Lysophosphatidic acid (LPA) is a membrane-derived lysophospholipid that exists in the plasma and platelets. It exerts its functions through activation of various LPA receptors (LPARs), which belong to the family of G protein-coupled receptors. Activation of LPARs has important roles in stem cell differentiation. However, how LPA affects human hematopoietic stem cell (HSC) differentiation remains elusive. In our previous studies, we have suggested that LPA receptor 2 (LPA2) and LPA receptor 3 (LPA3) play opposing roles and may act as a molecular switch during megakaryocytic differentiation in K562 cells. In this study, human CD34+ HSCs and zebrafish are adopted to investigate the roles of LPA3 during megakaryopoiesis/thrombopoiesis in vitro and in vivo. Our results show that LPAR3 mRNA expression level is decreased upon induction by thrombopoietin and stem cell factor in human HSCs. Using pharmacological activators and shRNA knockdown experiments, we demonstrate that activation of LPA3 inhibits megakaryopoiesis in human HSCs. In addition, pharmacological activation of LPA3 suppressed thrombopoiesis in zebrafish. Furthermore, blockage of LPA3 translation by morpholino increased the number of CD41-GFP+ cells in Tg(CD41:eGFP) zebrafish. Moreover, the mRNA expression level of zCD41 increased significantly in LPA3-knockout zebrafish. These results clarify the negative role of LPA3 during megakaryopoiesis and provide important information for potential treatments of related diseases, such as megakaryopenia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|