G protein coupled receptors in embryonic stem cells: a role for Gs-alpha signaling.
BACKGROUND
Identification of receptor mediated signaling pathways in embryonic stem (ES) cells is needed to facilitate strategies for cell replacement using ES cells. One large receptor family, largely uninvestigated in ES cells, is G protein coupled receptors (GPCRs). An important role for these receptors in embryonic development has been described, but little is known about GPCR expression in ES cells.


RESULTS
We have examined the expression profile of 343 different GPCRs in mouse ES cells demonstrating for the first time that a large number of GPCRs are expressed in undifferentiated and differentiating ES cells, and in many cases at high levels. To begin to define a role for GPCR signaling in ES cells, the impact of activating Gs-alpha, one of the major alpha subunits that couples to GPCRs, was investigated. Gs-alpha activation resulted in larger embryoid bodies (EBs), due, in part, to increased cell proliferation and prevented the time-related decline in expression of transcription factors important for maintaining ES cell pluripotency.


CONCLUSIONS
These studies suggest that Gs-alpha signaling contributes to ES cell proliferation and pluripotency and provide a framework for further investigation of GPCRs in ES cells.
Layden
Brian T
BT
Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Newman
Marsha
M
Chen
Fei
F
Fisher
Amanda
A
Lowe
William L
WL
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D043562:Receptors, G-Protein-Coupled; D002772:Cholera Toxin; D019205:GTP-Binding Protein alpha Subunits, Gs