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EMBRYONIC STEM CELLS

Lysophosphatidic Acid Inhibits Neuronal Differentiation of Neural Stem/Progenitor Cells Derived from Human Embryonic Stem Cells

^aCentre for Neuroscience and
^bDepartment of Pharmacology, University of Melbourne, Parkville, Victoria, Australia

Key Words. Embryonic stem cells • Embryonic stem cell biology • In vitro differentiation • Neural stem cell • Neural differentiation • Signal transduction

Correspondence: Alice Pébay, Ph.D., Centre for Neuroscience, University of Melbourne, Parkville 3010, Victoria, Australia. Telephone: 61383443899; Fax: 61393494432; e-mail: apebay{at}unimelb.edu.au

Received January 4, 2008; accepted for publication February 19, 2008.
First published online in STEM CELLS EXPRESS   February 28, 2008.



Lysophospholipids are signaling molecules that play broad and major roles within the nervous system during both early development and neural injury. We used neural differentiation of human embryonic stem cells (hESC) as an in vitro model to examine the specific effects of lysophosphatidic acid (LPA) at various stages of neural development, from neural induction to mature neurons and glia. We report that LPA inhibits neurosphere formation and the differentiation of neural stem cells (NSC) toward neurons, without modifying NSC proliferation, apoptosis, or astrocytic differentiation. LPA acts through the activation of the Rho/ROCK and the phosphatidylinositol 3-kinase/Akt pathways to inhibit neuronal differentiation. This study is the first demonstration of a role for LPA signaling in neuronal differentiation of hESC. As LPA concentrations increase during inflammation, the inhibition of neuronal differentiation by LPA might contribute to the low level of neurogenesis observed following neurotrauma.

Disclosure of potential conflicts of interest is found at the end of this article.