Expression of Wnt and Notch pathway genes in a pluripotent human embryonal carcinoma cell line and embryonic stem cells

Abstract

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.

Expression Profiling and Functional Analysis of Wnt Signaling Mechanisms in Mesenchymal Stem Cells

“…Previously published work has identified intracellular signaling mechanisms involved in osteogenic and adipogenic specification in MSC cultures [19], but relatively little is known about the regulatory inputs that enable the MSCs to maintain their undifferentiated phenotype or those that regulate its differentiation into specialized cell types. Recent expression profiling studies have identified key developmental signaling molecules, including Wnts, in pluripotent embryonic stem cell populations, suggesting that these fundamental cell-cell communication pathways may be instrumental in controlling "stemness" [20][21][22][23]. Here we have identified the expression profile of Wnt signaling molecules in MSCs, providing evidence for their involvement in both the maintenance and differentiation of adult mesenchymal progenitor cells.…”

Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells

“…Numerous signaling pathways play important roles in maintaining pluripotency during embryogenesis. For example, the Wnt signaling pathway has important roles in embryogenesis and cancer (20)(21)(22)(23). TGF-␤ signaling is necessary to maintain ES cell pluripotency, and PTEN signaling plays important roles in the maintenance of hematopoetic stem cell self-renewal.…”

Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis

“…[57][58][59] In comparison with 3 different microarray approaches 9,10,15 we estimated the overlap of genes in different fractions of murine and human HSCs. Among the genes that were up-regulated in several fractions were frizzled 6 (FZD6) that might function as a receptor for the Wnt-pathway, 60 RNA-binding protein with multiple splicing (RBPMS), MDR1, JAK3, and the homeodomain protein HOXA9. HOXA9 knockout mice showed defects in hematopoiesis, …”