Transcriptional program of bone morphogenetic protein-2-induced epithelial and smooth muscle differentiation of pluripotent human embryonal carcinoma cells Journal Article
| Authors: | Chadalavada, R. S. V.; Houldsworth, J.; Olshen, A. B.; Bosl, G. J.; Studer, L.; Chaganti, R. S. K. |
| Article Title: | Transcriptional program of bone morphogenetic protein-2-induced epithelial and smooth muscle differentiation of pluripotent human embryonal carcinoma cells |
| Abstract: | Pluripotent human embryonal carcinoma NTera2/cloneD1 (NT2/D1) cells respond to multiple vertebrate patterning factors and offer a unique model system to investigate the signaling events associated with lineage determination and cell differentiation. Here, we define the temporal changes in global gene expression patterns in NT2/D1 cells upon treatment with bone morphogenetic protein-2 (BMP-2). Exposure to BMP-2 rapidly induced the expression of several transcription factors involved in establishing non-neural ectodermal fate followed by the appearance of epithelial-specific markers. Subsequent loss of stem cell markers was coupled to gene expression changes associated with decreased proliferative activity. Temporal clustering of gene expression patterns revealed a concurrent down-regulation of multiple transcripts involved in neurogenesis, neurite outgrowth, and axonal guidance, suggesting that the BMP-mediated differentiation process involves pro-epithelial as well as anti-neurogenic mechanisms. In addition, increased expression of smooth muscle markers both by gene expression and immunohistochemistry was detected. Several neural crest markers were induced preceding such a differentiation, compatible with a neural crest origin of NT2/D1-derived smooth muscle cells. Comparison of changes in transcript expression between BMP-2-induced epithelial versus all-trans-retinoic acid (ATRA)-induced neural differentiation revealed potential candidates for regulation of BMP-2 signaling and suppression of neural fate by BMP-2. This study suggests that BMP-2-induced differentiation of NT2/D1 cells provides a powerful assay to study early human epithelial and smooth muscle development. © Springer-Verlag 2005. |
| Keywords: | immunohistochemistry; signal transduction; controlled study; human cell; cell proliferation; biological markers; reproducibility of results; gene expression; gene expression profiling; transforming growth factor beta; cell line; transcription factor; cell fate; embryo pattern formation; genetic transcription; cell differentiation; transcription, genetic; cell lineage; vertebrata; gene expression regulation; oligonucleotide array sequence analysis; nerve fiber; epithelial cells; neural crest; pluripotent stem cell; pluripotent stem cells; bone morphogenetic protein 2; epithelium; cell marker; cell clone; nerve cell differentiation; nervous system development; vertebrate; retinoic acid; embryonal carcinoma; carcinoma cell; differentiation; smooth muscle; bone morphogenetic proteins; ectoderm; tretinoin; atra; nerve fiber growth; myocytes, smooth muscle; bmp-2; tumor stem cells; micro-array |
| Journal Title: | Functional and Integrative Genomics |
| Volume: | 5 |
| Issue: | 2 |
| ISSN: | 1438-793X |
| Publisher: | Springer Verlag |
| Date Published: | 2005-04-01 |
| Start Page: | 59 |
| End Page: | 69 |
| Language: | English |
| DOI: | 10.1007/s10142-005-0132-7 |
| PUBMED: | 15690164 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 24 October 2012" - "CODEN: FIGUB" - "Source: Scopus" |
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10Chadalavada -
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220Studer -
391Chaganti -
430Bosl
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