Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis.
Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation.
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell biology Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Chinese Academy of Sciences, Shanghai, China.
Haisen
H
Li
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell biology Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Chinese Academy of Sciences, Shanghai, China Howard Hughes Medical Institute Children's Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Rui
R
Yue
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell biology Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Chinese Academy of Sciences, Shanghai, China.
Bin
B
Wei
Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences Peking University, Beijing, China.
Ge
G
Gao
Institute of Neuroscience and State Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences, Shanghai, China.
Jiulin
J
Du
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell biology Shanghai Institutes for Biological Sciences Graduate School of the Chinese Academy of Sciences Chinese Academy of Sciences, Shanghai, China Shanghai Key Laboratory of Signaling and Disease Research School of Life Science and Technology Tongji University, Shanghai, China gpei@sibs.ac.cn peigang@tongji.edu.cn.
Gang
G
Pei
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D047108:Embryonic Development / Q000502:physiology*; D005434:Flow Cytometry; D055018:Hemangioblasts / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology; D017403:In Situ Hybridization; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D008856:Microscopy, Fluorescence; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish; D000099189:Lysophospholipase D
D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid
LPA; embryonic stem cell; hemangioblast; hematopoiesis; zebrafish