Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology.

Published online

Journal Article

BACKGROUND: Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP) cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. RESULTS: Our results demonstrate that Lysophosphatidic Acid (LPA) and Sphingosine-1-phosphate (S1P) receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to G i/o G-proteins that inhibit adenylyl cyclase and to G q-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via G i/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR)- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. CONCLUSION: Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

Full Text

Duke Authors

Cited Authors

  • Hurst, JH; Mumaw, J; Machacek, DW; Sturkie, C; Callihan, P; Stice, SL; Hooks, SB

Published Date

  • December 11, 2008

Published In

Volume / Issue

  • 9 /

Start / End Page

  • 118 -

PubMed ID

  • 19077254

Pubmed Central ID

  • 19077254

Electronic International Standard Serial Number (EISSN)

  • 1471-2202

Digital Object Identifier (DOI)

  • 10.1186/1471-2202-9-118

Language

  • eng

Conference Location

  • England