Transcriptional program of bone morphogenetic protein-2-induced epithelial and smooth muscle differentiation of pluripotent human embryonal carcinoma cells

被引：21

作者：

Chadalavada R.S.V. ^{[1
,6
]}

Houldsworth J. ^{[1
,2
,6
]}

Olshen A.B. ^{[3
]}

Bosl G.J. ^{[2
,6
]}

Studer L. ^{[4
,5
,6
]}

Chaganti R.S.K. ^{[1
,2
,6
]}

机构：

[1] Cell Biology Program, Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

[2] Department of Medicine, Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

[3] Dept. of Epidemiology/Biostatistics, Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

[4] Developmental Biology Program, Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

[5] Division of Neurosurgery, Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

[6] Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

来源：

Functional & Integrative Genomics | 2005年 / 5卷 / 2期

基金：

美国国家卫生研究院;

关键词：

BMP-2; Differentiation; Embryonal carcinoma; Micro-array;

D O I：

10.1007/s10142-005-0132-7

中图分类号：

学科分类号：

摘要：

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.

引用

页码：59 / 69

页数：10

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