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Transient inhibition of BMP signaling by Noggin induces cardiomyocyte differentiation of mouse embryonic stem cells

  • A Corrigendum to this article was published on 01 July 2005

Abstract

Embryonic stem (ES) cells are a promising source of cardiomyocytes, but clinical application of ES cells has been hindered by the lack of reliable selective differentiation methods. Differentiation into any lineage is partly dependent on the regulatory mechanisms of normal early development. Although several signals, including bone morphogenetic protein (BMP)1,2, Wnt3 and FGF4, are involved in heart development, scarce evidence is available about the exact signals that mediate cardiomyocyte differentiation. While investigating the involvement of BMP signaling in early heart formation in the mouse, we found that the BMP antagonist Noggin is transiently but strongly expressed in the heart-forming region during gastrulation and acts at the level of induction of mesendoderm to establish conditions conducive to cardiogenesis. We applied this finding to develop an effective protocol for obtaining cardiomyocytes from mouse ES cells by inhibition of BMP signaling.

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Acknowledgements

This work was (partially) supported by a grant-in-aid from the 21st century Center of Excellence Program of the Ministry of Education, Culture, Sports, Science and Technology, Japan to Keio University. We are grateful to H. Niwa for kindly providing ES cell line EB3 and T. Yoshizaki and Y. Okada for their thoughtful advice and discussion.

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Competing interests

The authors declare no competing financial interests.

Correspondence to Keiichi Fukuda.

Supplementary information

Supplementary Fig. 1

Dose-efficiency relationship of Noggin administration was demonstrated using R1 ES cell lines. (PDF 89 kb)

Supplementary Table 1

PCR primers used in this study (PDF 50 kb)

Supplementary Video

Noggin-treated beating embryoid body (MOV 2592 kb)

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Figure 1: Transient expression of noggin at the heart forming area.
Figure 2: Protocol and efficiency of the cardiomyocyte induction from ES cells using noggin, chordin and soluble BMP receptor-1A.
Figure 3: Expression of stem cell marker, cardiac transcription factors and cardiac specific proteins in noggin-treated ES cells.