Expression of Wnt and Notch pathway genes in a pluripotent human embryonal carcinoma cell line and embryonic stem cell.
Embryonal carcinoma (EC) cells, the pluripotent stem cells of teratocarcinomas, show many similar-ities to embryonic stem (ES) cells. Since EC cells are malignant but their terminally differentiated derivatives are not, understanding the molecular mechanisms that regulate their differentiation maybe of value for diagnostic and therapeutic purposes. We have examined the expression of multiple components of two developmentally important cell-cell signalling pathways, Wnt and Notch, in the pluripotent human EC cell line, NTERA2, and the human ES cell line, H7. Both pathways have well-documented roles in controlling neurogenesis, a process that occurs largely in response to retinoicacid (RA) treatment of NTERA2 cultures and spontaneously in H7 cultures. In NTERA2, many ofthe genes tested showed altered transcriptional regulation following treatment with RA. These include members of the frizzled gene family (FZDI, FZD3, FZD4, FZD5, FZD6), encoding receptors forWnt proteins, the Frizzled Related Protein family (SFRPI, SFRP2, FRZB, SFRP4), encoding solubleWnt antagonists and also ligands and receptors of the Notch pathway (Dlkl, Jaggedl; Notchl, Notch2, Notch3). Few differences were found in the repertoire of Wnt and Notch pathway genes expressed by NTERA2 EC cells and H7 ES cells. We present a model in which interactions between and regulation of Wnt and Notch signalling are important in maintaining EC/ES stem cells and also controlling their differentiation.
Walsh
James
J
Department of biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.
Andrews
Peter W
PW
D018236:Carcinoma, Embryonal / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D038702:Follistatin-Related Proteins / Q000096:biosynthesis; D051157:Frizzled Receptors; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins; D000094742:Secreted Frizzled-Related Proteins
D038702:Follistatin-Related Proteins; D051157:Frizzled Receptors; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D014157:Transcription Factors; D014212:Tretinoin; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000099274:Frizzled-Related Proteins; C105574:FZD3 protein, human; C486339:Fzd3 protein, mouse; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; C499374:NOTCH3 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins; C498454:Sfrp4 protein, mouse