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Open Access Research

Transcriptomic and phenotypic analysis of murine embryonic stem cell derived BMP2+ lineage cells: an insight into mesodermal patterning

Michael Xavier Doss1, Shuhua Chen1, Johannes Winkler1, Rita Hippler-Altenburg1, Margareta Odenthal2, Claudia Wickenhauser2, Sridevi Balaraman2, Herbert Schulz3, Oliver Hummel3, Norbert Hübner3, Nandini Ghosh-Choudhury4, Isaia Sotiriadou1, Jürgen Hescheler1 and Agapios Sachinidis1*

Author Affiliations

1 Institute of Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany

2 Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany

3 Max-Delbrueck-Center for Molecular Medicine - MDC, Robert-Rössle Str. 10, 13092 Berlin, Germany

4 Department of Pathology, The University of Texas Health Science Center at San Antonio, TX 78229, USA

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Genome Biology 2007, 8:R184  doi:10.1186/gb-2007-8-9-r184

Published: 4 September 2007

Abstract

Background

Bone morphogenetic protein (BMP)2 is a late mesodermal marker expressed during vertebrate development and plays a crucial role in early embryonic development. The nature of the BMP2-expressing cells during the early stages of embryonic development, their transcriptome and cell phenotypes developed from these cells have not yet been characterized.

Results

We generated a transgenic BMP2 embryonic stem (ES) cell lineage expressing both puromycin acetyltransferase and enhanced green fluorescent protein (EGFP) driven by the BMP2 promoter. Puromycin resistant and EGFP positive BMP2+ cells with a purity of over 93% were isolated. Complete transcriptome analysis of BMP2+ cells in comparison to the undifferentiated ES cells and the control population from seven-day-old embryoid bodies (EBs; intersection of genes differentially expressed between undifferentiated ES cells and BMP2+ EBs as well as differentially expressed between seven-day-old control EBs and BMP2+ EBs by t-test, p < 0.01, fold change >2) by microarray analysis led to identification of 479 specifically upregulated and 193 downregulated transcripts. Transcription factors, apoptosis promoting factors and other signaling molecules involved in early embryonic development are mainly upregulated in BMP2+ cells. Long-term differentiation of the BMP2+ cells resulted in neural crest stem cells (NCSCs), smooth muscle cells, epithelial-like cells, neuronal-like cells, osteoblasts and monocytes. Interestingly, development of cardiomyocytes from the BMP2+ cells requires secondary EB formation.

Conclusion

This is the first study to identify the complete transcriptome of BMP2+ cells and cell phenotypes from a mesodermal origin, thus offering an insight into the role of BMP2+ cells during embryonic developmental processes in vivo.