Genome-wide expression profile of first trimester villous and extravillous human trophoblast cells.
Bottom Line: We have examined the transcriptional changes associated with differentiation from villous to extravillous trophoblast using a whole genome microarray.We show that decidual T-cells, macrophages and NK cells express the inhibitory collagen receptor LAIR-1 and that EVT secrete LAIR-2, which can block this interaction.Since LAIR-2 is detectable in the urine of pregnant, but not non-pregnant women, trophoblast-derived LAIR-2 may also have systemic effects during pregnancy.
Affiliation: Department of Pathology and Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.Show MeSH
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Mentions: Comparison of the expression profiles of EVT and VT identified 3471 probes with q < 0.01 (FDR 1%) indicating differential expression. When classified into functional categories based on either GO annotation or KEGG pathways, over-representation analysis revealed that the most significantly up-regulated GO biological processes in EVT included ‘cell motion’ (63 transcripts), ‘immune response’ (71 transcripts) and ‘leukocyte adhesion’ (7 transcripts) (p < 0.0025, Supplementary Table 1). The most significantly down-regulated processes in EVT included metabolic processes such as ‘lipid metabolism’ and ‘fatty acid oxidation’ as well as ‘negative regulators of cell differentiation’. Specific functions represented by these transcripts were identified using the KEGG pathways which include known functional relationships between transcripts. Significantly up-regulated (p < 0.01) KEGG pathways included focal adhesion, extracellular matrix (ECM) receptor interactions, leukocyte transendothelial migration and cancer, whereas down-regulated pathways included amino acid metabolism, fatty acid metabolism and biosynthesis of steroids (Supplementary Table 2). These results show that as VT differentiate to EVT, there is co-ordinated up and down-regulation of specific pathways. The very significant up-regulation of more than 40 transcripts involved in the focal adhesion kinase (FAK) and ECM-receptor pathways, which are linked through the integrin receptors, clearly identifies a potentially important role for the focal adhesion kinase (PTK2) (Fig. 2). Several members of this pathway that are involved in cell proliferation are down-regulated on differentiation to EVT (VAV, JUNand CYCD). The FAK pathway also integrates transcripts involved in transducing signals that enhance cell migration (PAK, MLC, ACTN4), and these are up-regulated in EVT. Thus, this pathway offers novel insights into how FAK might be involved in the transition from proliferation in VT to post-mitotic, migratory EVT. Even in functions that have been well studied, such as migration, or ECM/receptor interactions we provide novel and more detailed information regarding the specific transcriptional changes underlying known differences in trophoblast function (Suppl Table 4).
Affiliation: Department of Pathology and Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.