Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells

Rajendrakumar S V Chadalavada, James Korkola, Jane Houldsworth, Adam B. Olshen, George J. Bosl, Lorenz Studer, R. S K Chaganti

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Human embryonal carcinoma (EC) cell lines exhibit considerable heterogeneity in their levels of pluripotency. Thus, NT2/D1 cells differentiate into neural lineages upon exposure to all-trans retinoic acid (ATRA) and non-neural epithelial lineages upon exposure to bone morphogenetic protein-2 (BMP-2). In contrast, 27X-1 cells differentiate into extra-embryonic endodermal (ExE) cells upon treatment with either morphogen. To understand the molecular basis for the differential responses of the two cell lines, we performed gene expression profiling at the undifferentiated EC cell line state to identify constitutive differences in gene expression. NT2/D1 cells preferentially expressed transcripts associated with neurectodermal development, whereas 27X-1 cells expressed high levels of transcripts associated with mesendodermal characteristics. We then determined temporal expression profiles of 27X-1 cells during ExE differentiation upon treatment with ATRA and BMP-2 and compared the data with changes in gene expression observed during BMP-2- and ATRA-induced differentiation of NT2/D1 cells. ATRA and BMP-2 induced distinct sets of transcription factors and phenotypic markers in the two EC cell lines, underlying distinct lineage choices. Although 27X-1 differentiation yielded comprehensive gene expression profiles of parietal endodermal lineages, we were able to use the combined analysis of 27X-1 data with data derived from yolk sac tumors for the identification of transcripts associated with visceral endoderm formation. Our results demonstrate constitutive differences in the levels of pluripotency between NT2/D1 and 27X-1 cells that correlate with lineage potential. This study also demonstrates that EC cells can serve as robust models to investigate early lineage choices during both embryonic and extra-embryonic human development.

Original languageEnglish (US)
Pages (from-to)771-778
Number of pages8
JournalStem Cells
Volume25
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Embryonal Carcinoma Stem Cells
Gene Expression
Bone Morphogenetic Protein 2
Tretinoin
Cell Line
Endodermal Sinus Tumor
Endoderm
Human Development
Gene Expression Profiling
Transcriptome
Embryonic Development
Transcription Factors
Carcinoma

Keywords

  • ATRA
  • BMP-2
  • Embryonal carcinoma
  • Germ cell tumors
  • Pluripotent
  • Yolk sac cell

ASJC Scopus subject areas

  • Cell Biology

Cite this

Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells. / Chadalavada, Rajendrakumar S V; Korkola, James; Houldsworth, Jane; Olshen, Adam B.; Bosl, George J.; Studer, Lorenz; Chaganti, R. S K.

In: Stem Cells, Vol. 25, No. 3, 03.2007, p. 771-778.

Research output: Contribution to journalArticle

Chadalavada, Rajendrakumar S V ; Korkola, James ; Houldsworth, Jane ; Olshen, Adam B. ; Bosl, George J. ; Studer, Lorenz ; Chaganti, R. S K. / Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells. In: Stem Cells. 2007 ; Vol. 25, No. 3. pp. 771-778.
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AU - Olshen, Adam B.

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N2 - Human embryonal carcinoma (EC) cell lines exhibit considerable heterogeneity in their levels of pluripotency. Thus, NT2/D1 cells differentiate into neural lineages upon exposure to all-trans retinoic acid (ATRA) and non-neural epithelial lineages upon exposure to bone morphogenetic protein-2 (BMP-2). In contrast, 27X-1 cells differentiate into extra-embryonic endodermal (ExE) cells upon treatment with either morphogen. To understand the molecular basis for the differential responses of the two cell lines, we performed gene expression profiling at the undifferentiated EC cell line state to identify constitutive differences in gene expression. NT2/D1 cells preferentially expressed transcripts associated with neurectodermal development, whereas 27X-1 cells expressed high levels of transcripts associated with mesendodermal characteristics. We then determined temporal expression profiles of 27X-1 cells during ExE differentiation upon treatment with ATRA and BMP-2 and compared the data with changes in gene expression observed during BMP-2- and ATRA-induced differentiation of NT2/D1 cells. ATRA and BMP-2 induced distinct sets of transcription factors and phenotypic markers in the two EC cell lines, underlying distinct lineage choices. Although 27X-1 differentiation yielded comprehensive gene expression profiles of parietal endodermal lineages, we were able to use the combined analysis of 27X-1 data with data derived from yolk sac tumors for the identification of transcripts associated with visceral endoderm formation. Our results demonstrate constitutive differences in the levels of pluripotency between NT2/D1 and 27X-1 cells that correlate with lineage potential. This study also demonstrates that EC cells can serve as robust models to investigate early lineage choices during both embryonic and extra-embryonic human development.

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