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Editorial
. 2016 Aug 2:3:33.
doi: 10.21037/sci.2016.07.03. eCollection 2016.

WNT and BMP regulate roadblocks toward cardiomyocyte differentiation: lessons learned from embryos inform human stem cell differentiation

Andrea Münsterberg  1 , Stefan Hoppler  2
Affiliations
Editorial

WNT and BMP regulate roadblocks toward cardiomyocyte differentiation: lessons learned from embryos inform human stem cell differentiation

Andrea Münsterberg et al. Stem Cell Investig. .
No abstract available

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Roadblocks toward Cardiac Development. Schematic description of the cardiomyocyte differentiation protocol from pluripotent (PLURI) embryonic stem cells via mesoderm induction (MESO) to differentiated cardiomyocytes (CARDIO). (A) WNT/β-catenin signaling and BMP/SMAD1 signaling promote mesoderm induction, but WNT/β-catenin signaling subsequently restricts cardiomyocyte differentiation. Many cardiomyocyte differentiation protocols therefore combine early activation of WNT and/or BMP signaling with later inhibition of Wnt signaling; (B) SOX2 serves as a roadblock early on the path from pluripotent to mesoderm fate, then MSX1, CDX1 and CDX2 serve as roadblocks on the path from mesoderm to cardiomyocyte differentiation. Early WNT and BMP signaling remove the SOX2 roadblock, but later WNT signaling would maintain the MSX/CDX roadblock, if it were not inhibited. Rather than just roadblocks preventing cardiomyocyte development, SOX2 and MSX/CDX probably function to promote differentiation into alternative cell fates; (C) the negative regulation of SOX2 by BMP and by WNT signaling are both indirect and function in parallel. BMP regulation is faster, involving upregulation of the microRNA miR-877, which targets SOX2 transcripts directly; while WNT signaling regulates EOMES, which represses SOX2 transcription after a delay. Figure adapted from (1).
Figure 2
Figure 2
Cardiac corridor is defined by WNT and BMP input. Patterning map for hESC culture represented by a two-dimensional grid indicating high to low WNT signaling activity from top to bottom; and low to high BMP signaling activity from left to right. Cardiac induction is promoted by the combined input from WNT and BMP signaling activity during the early stages of differentiation. Cardiac development is induced by medium WNT activity combined with medium BMP activity but also with low WNT/high BMP; and high WNT/low BMP conditions. This pattern defines a diagonal corridor where cardiac induction occurs. Alternative fates are clearly delineated by high BMP and medium to high WNT activity (other mesodermal fates) and by low WNT and low BMP activity, but there is less clear delineation between cardiac and endodermal fates under low BMP and intermediate WNT activity conditions. Figure adapted from (1). hESC, human embryonic stem cell.
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References

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