Global gene expression patterns during differentiation of F9 embryonal carcinoma cells into parietal endoderm

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Abstract

Expression levels of over 8,900 murine genes were examined, using cDNA microarrays, during the differentiation of F9 cells into parietal endoderm following exposure to retinoic acid/dibutyryl cAMP. Gene induction and repression over the time course exhibited a biphasic pattern consistent with a transition from undifferentiated F9 cells to primitive endoderm and finally parietal endoderm. A 6-h induction with retinoic acid/cAMP/cycloheximide resulted in 109 candidate immediate response genes. During a 9-day time course 516 genes were selected as being significantly induced/repressed. Several of these genes had been previously identified as having altered expression patterns in F9 cells undergoing differentiation by retinoic acid/cAMP. Functional characterization of these genes demonstrated that the majority were transcription factors while others included surface antigens and genes involved in intracellular transport. Cluster analysis, utilizing both a hierarchical algorithm and self-organizing map, resulted in very similar gene clusters. Our studies revealed an extremely complex set of interacting signals that decide between cell death, differentiation, cell cycle withdrawal, and ultimately the traits associated with the terminal differentiated parietal endoderm cell type. The sets of genes identified here can now be modulated in a rational way to try to understand their role in differentiation.

Original languageEnglish (US)
Pages (from-to)105-119
Number of pages15
JournalFunctional and Integrative Genomics
Volume2
Issue number3
DOIs
StatePublished - 2002

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Embryonal Carcinoma Stem Cells
Endoderm
Gene Expression
Genes
Tretinoin
Cell Differentiation
Cycloheximide
Surface Antigens
Multigene Family
Oligonucleotide Array Sequence Analysis
Cluster Analysis
Cell Cycle
Cell Death
Transcription Factors

Keywords

  • F9
  • Microarray
  • Parietal endoderm
  • Retinoic acid

ASJC Scopus subject areas

  • Genetics

Cite this

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abstract = "Expression levels of over 8,900 murine genes were examined, using cDNA microarrays, during the differentiation of F9 cells into parietal endoderm following exposure to retinoic acid/dibutyryl cAMP. Gene induction and repression over the time course exhibited a biphasic pattern consistent with a transition from undifferentiated F9 cells to primitive endoderm and finally parietal endoderm. A 6-h induction with retinoic acid/cAMP/cycloheximide resulted in 109 candidate immediate response genes. During a 9-day time course 516 genes were selected as being significantly induced/repressed. Several of these genes had been previously identified as having altered expression patterns in F9 cells undergoing differentiation by retinoic acid/cAMP. Functional characterization of these genes demonstrated that the majority were transcription factors while others included surface antigens and genes involved in intracellular transport. Cluster analysis, utilizing both a hierarchical algorithm and self-organizing map, resulted in very similar gene clusters. Our studies revealed an extremely complex set of interacting signals that decide between cell death, differentiation, cell cycle withdrawal, and ultimately the traits associated with the terminal differentiated parietal endoderm cell type. The sets of genes identified here can now be modulated in a rational way to try to understand their role in differentiation.",
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AB - Expression levels of over 8,900 murine genes were examined, using cDNA microarrays, during the differentiation of F9 cells into parietal endoderm following exposure to retinoic acid/dibutyryl cAMP. Gene induction and repression over the time course exhibited a biphasic pattern consistent with a transition from undifferentiated F9 cells to primitive endoderm and finally parietal endoderm. A 6-h induction with retinoic acid/cAMP/cycloheximide resulted in 109 candidate immediate response genes. During a 9-day time course 516 genes were selected as being significantly induced/repressed. Several of these genes had been previously identified as having altered expression patterns in F9 cells undergoing differentiation by retinoic acid/cAMP. Functional characterization of these genes demonstrated that the majority were transcription factors while others included surface antigens and genes involved in intracellular transport. Cluster analysis, utilizing both a hierarchical algorithm and self-organizing map, resulted in very similar gene clusters. Our studies revealed an extremely complex set of interacting signals that decide between cell death, differentiation, cell cycle withdrawal, and ultimately the traits associated with the terminal differentiated parietal endoderm cell type. The sets of genes identified here can now be modulated in a rational way to try to understand their role in differentiation.

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