Submitted on January 4, 2008
Accepted on February 19, 2008
Lysophosphatidic Acid Inhibits Neuronal Differentiation of Neural Stem/progenitor Cells Derived from Human Embryonic Stem Cells
Mirella Dottori 1,
Jessie Leung 2,
Ann M. Turnley 2,
Alice Pébay 1*
1 Centre for Neuroscience and Department of Pharmacology, the University of Melbourne, Parkville VIC 3010, Australia
2 Centre for Neuroscience the University of Melbourne, Parkville VIC 3010, Australia
* To whom correspondence should be addressed. E-mail: apebay{at}unimelb.edu.au.
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Abstract |
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Lysophospholipids are signalling molecules that play broad and major roles within the nervous system both during 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) towards neurons, without modifying NSC proliferation, apoptosis or astrocytic differentiation. LPA acts through the activation of the Rho/ROCK and the PI3K/Akt pathways to inhibit neuronal differentiation. This study is the first demonstration of a role for LPA signalling 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.
Key Words.
Embryonic stem cells, Embryonic stem cell biology, In vitro differentiation, Neural stem cell, Neural differentiation, Signal transduction
