Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

EMBO J. 2014 Jun 17;33(12):1383-96. doi: 10.15252/embj.201387594. Epub 2014 May 14.


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.

Keywords: LPA; embryonic stem cell; hemangioblast; hematopoiesis; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Embryonic Development / physiology*
  • Flow Cytometry
  • Hemangioblasts / physiology*
  • Hematopoiesis / drug effects*
  • Hematopoiesis / physiology
  • In Situ Hybridization
  • Lysophospholipids / pharmacology*
  • Mice
  • Microscopy, Fluorescence
  • Phosphoric Diester Hydrolases / metabolism
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Lysophosphatidic Acid / metabolism
  • Signal Transduction / physiology*
  • Zebrafish


  • Lysophospholipids
  • RNA, Small Interfering
  • Receptors, Lysophosphatidic Acid
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase
  • lysophosphatidic acid