Abstract
BackgroundThe trophoblast lineage arises as the first differentiation event during embryogenesis. Trophoblast giant cells are one of several end-stage products of trophoblast cell differentiation in rodents. These cells are located at the maternal-fetal interface and are capable of invasive and endocrine functions, which are necessary for successful pregnancy. Rcho-1 trophoblast stem cells can be effectively used as a model for investigating trophoblast cell differentiation. In this report, we evaluated the role of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in the regulation of trophoblast cell differentiation. Transcript profiles from trophoblast stem cells, differentiated trophoblast cells, and differentiated trophoblast cells following disruption of PI3K signaling were generated and characterized.ResultsProminent changes in gene expression accompanied the differentiation of trophoblast stem cells. PI3K modulated the expression of a subset of trophoblast cell differentiation-dependent genes. Among the PI3K-responsive genes were those encoding proteins contributing to the invasive and endocrine phenotypes of trophoblast giant cells.ConclusionsGenes have been identified with differential expression patterns associated with trophoblast stem cells and trophoblast cell differentiation; a subset of these genes are regulated by PI3K signaling, including those impacting the differentiated trophoblast giant cell phenotype.
Highlights
The trophoblast lineage arises as the first differentiation event during embryogenesis
All DNA microarray data presented in this report are deposited in the Gene Expression Omnibus (GEO) repository under the GSE21938 accession number http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi? acc=GSE21938
Trophoblast stem-associated genes Approximately half of the genes differentially expressed between the stem cell- and differentiated cell-states were specific to the stem cell state, termed ‘trophoblast stem cell-associated’ genes
Summary
The trophoblast lineage arises as the first differentiation event during embryogenesis. Trophoblast giant cells are one of several end-stage products of trophoblast cell differentiation in rodents. These cells are located at the maternal-fetal interface and are capable of invasive and endocrine functions, which are necessary for successful pregnancy. One compartment contains trophoblast cells specialized for interactions with the maternal environment, while the other contains trophoblast cells directed toward the bidirectional transport of nutrients and wastes between the mother and the fetus. Cell lineages directed toward the maternal environment, include trophoblast giant cells, spongiotrophoblast, glycogen cells, and invasive trophoblast cells; whereas syncytial trophoblast regulate maternal-fetal nutrient and waste delivery [1,2,3]. Each lineage possesses specialized functions necessary for a normal pregnancy
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