Journal
GENE EXPRESSION PATTERNS
Volume 21, Issue 2, Pages 103-110Publisher
ELSEVIER
DOI: 10.1016/j.gep.2016.05.001
Keywords
Trophoblast; Tube formation; Angiogenesis; Microarray; Weighted correlation network analysis
Categories
Funding
- National Health and Medical Research Council (NHMRC) of Australia
- NHMRC [GNT565320, GNT1020749]
- NHMRC Australian Biomedical Training Fellowship [GNT1012784]
- Adelaide Scholarship International award
- Healthy Development Adelaide and Channel 7 Children's Research Foundation PhD Scholarship
- Australian Postgraduate Award
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Extravillous cytotrophoblasts isolated from first trimester placenta, and immortalised cell lines derived from them, have the intrinsic ability to form endothelial-like tubes when cultured on Matrigel (TM) extracellular matrix. This in vitro tube formation may model placental angiogenesis and/or endovascular differentiation by trophoblasts. To interpret the relevance of this phenomenon to placental development, we used a gene expression microarray approach to identify which genes and pathways are associated with the tube-forming phenotype of HTR8/SVneo first trimester trophoblasts (HTR8-M), compared with HTR8/SVneo not forming tubes on plastic culture surface (HTR8-P). Furthermore, we used weighted gene co-expression network analysis (WGCNA) of microarray data to identify modules of co-expressed genes underlying the biological processes. There were 481 genes differentially expressed between HTR8-M and HTR8-P and these were significantly enriched for blood vessel development and related gene ontologies. WGCNA clustered the genes into 9 co-expression modules. One module was significantly associated with HTR8-M (p = 1.15E-05) and contained genes involved in actin cytoskeleton organization, cell migration and blood vessel development, consistent with tube formation on Matrigel. Another module was significantly associated with HTR8-P (p = 1.94E-05) and was enriched for genes involved in mitosis, consistent with proliferation by cells on plastic which do not differentiate. Up-regulation of angiogenesis and vascular development pathways in endovascular trophoblasts in vivo could underpin spiral artery remodelling processes, which are defective in preeclamptic pregnancies. (C) 2016 Elsevier B.V. All rights reserved.
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