%0 Journal Article
%T Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology
%A Jillian H Hurst
%A Jennifer Mumaw
%A David W Machacek
%A Carla Sturkie
%A Phillip Callihan
%A Steve L Stice
%A Shelley B Hooks
%J BMC Neuroscience
%D 2008
%I BioMed Central
%R 10.1186/1471-2202-9-118
%X 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 Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/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.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.We have previously generated a stable neuroepithelial (NEP) cell line derived from human embryonic stem (hES) cells (hES-NEP) that is grown under adherent conditions, is self-renewing, and stably maintains capacity for neuronal or glial differentiation. These hES-NEP cells recapitulate morphological and phenotypic features of neural progenitor cells isolated from fetal tissue [1]. Such a cell line has potential both as a source for specific neuronal lineages to be used in hES cell neural therapy and as an in vitro model system in which to study human NEP cell function and its regulation by signaling mediators such as lysophospholipids. The lysophospholipid signaling mediators Lysophosphatidic Acid (LPA) and Sphingosine 1-phosphate (S1P) are critical regulators of neural development, modulating neural growth, morphogenesis, and differentiation.Lysophospholipid signaling has been implicated in mediatin
%U http://www.biomedcentral.com/1471-2202/9/118