PUBLICATION
Activation of Lysophosphatidic Acid Receptor 3 Inhibits Megakaryopoiesis in Human Hematopoietic Stem Cells and Zebrafish
- Authors
- Lin, K.H., Li, M.W., Chang, Y.C., Lin, Y.N., Ho, Y.H., Weng, W.C., Huang, C.J., Chang, B.E., Yao, C.L., Lee, H.
- ID
- ZDB-PUB-171215-5
- Date
- 2017
- Source
- Stem cells and development 27(3): 216-224 (Journal)
- Registered Authors
- Chang, Bei-En, Huang, Chang-Jen, Lee, Hsinyu
- Keywords
- none
- MeSH Terms
-
- Animals
- Receptors, Lysophosphatidic Acid/antagonists & inhibitors
- Receptors, Lysophosphatidic Acid/genetics
- Receptors, Lysophosphatidic Acid/metabolism*
- Megakaryocytes/metabolism*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Thrombopoiesis*
- Hematopoietic Stem Cells/metabolism*
- Humans
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29239275 Full text @ Stem Cells Dev.
Citation
Lin, K.H., Li, M.W., Chang, Y.C., Lin, Y.N., Ho, Y.H., Weng, W.C., Huang, C.J., Chang, B.E., Yao, C.L., Lee, H. (2017) Activation of Lysophosphatidic Acid Receptor 3 Inhibits Megakaryopoiesis in Human Hematopoietic Stem Cells and Zebrafish. Stem cells and development. 27(3):216-224.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping