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

  

Authors:	Chadalavada, R. S. V.; Korkola, J. E.; Houldsworth, J.; Olshen, A. B.; Bosl, G. J.; Studer, L.; Chaganti, R. S. K.
Article Title:	Constitutive gene expression predisposes morphogen-mediated cell fate responses of NT2/D1 and 27X-1 human embryonal carcinoma cells
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. ©AlphaMed Press.
Keywords:	controlled study; human cell; flow cytometry; gene expression; gene expression profiling; morphogen; cell fate; morphogenesis; cell differentiation; cell line, tumor; gene expression regulation, neoplastic; kinetics; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; pluripotent; bone morphogenetic protein 2; nucleic acid hybridization; oligopeptides; germ cell tumors; rna, neoplasm; retinoic acid; embryonal carcinoma; neuroectoderm; tretinoin; atra; carcinoma, embryonal; bmp-2; yolk sac cell
Journal Title:	Stem Cells
Volume:	25
Issue:	3
ISSN:	1066-5099
Publisher:	AlphaMed Press
Date Published:	2007-03-01
Start Page:	771
End Page:	778
Language:	English
DOI:	10.1634/stemcells.2006-0271
PUBMED:	17138961
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33847641528&partnerID=40&md5=01f0f9c4c43fca6cca74c2751a3f122e
Notes:	--- - "Cited By (since 1996): 2" - "Export Date: 17 November 2011" - "CODEN: STCEE" - "Source: Scopus"

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