The F9 teratocarcinoma cell line is a well-documented model system in primary cell lineage differentiation. After exposure to trans-retinoic acid, these cells can develop into two distinct forms of extra-embryonic endoderm. To date, differential library screening has been the best tool available to study the numerous events occurring during the transformation from an undifferentiated tumor cell line into a fully differentiated endoderm derivative. The advent of DNA microarray technology now allows the ability to examine the changes in RNA levels of a very large number of genes simultaneously.
The differential expression profile of F9 embryonal carcinoma cells was studied during their differentiation into parietal endoderm after exposure to 10−7 M retinoic acid (RA) and 10−3 M Dibutyryl cyclic AMP. We examined the expression profile of the cells after induction for: 4, 8 and 16 hours as well as 1, 3, 4, 5, 7, 9 and 14 days, on microarrays containing 5700 mouse cDNA clones. Our results indicate two major stages in the course of differentiation into parietal endoderm. In the first 24 hours, the cells turn off many markers that are specific for several types of tissues, which are derivatives of all three primary cell types. They also show induction of several transcription factors, nucleases, proteinases and activators/inhibitors of several signal transduction pathways. Around the third day, they begin to express gene products that are associated with the final endodermal cell types.
This is a preview of subscription content, access via your institution
