Key publications

UQ Centre for Cardiac and Vascular Biology Publications


 

Beating human heart cells from endothelium

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Beating human heart cells from endothelium

Abstract
During vertebrate development, mesodermal fate choices are regulated by interactions between morphogens such as activin/nodal, BMPs and Wnt/β-catenin that define anterior-posterior patterning and specify downstream derivatives including cardiomyocyte, endothelial and hematopoietic cells. We used human embryonic stem cells to explore how these pathways control mesodermal fate choices in vitro. Varying doses of activin A and BMP4 to mimic cytokine gradient polarization in the anterior-posterior axis of the embryo led to differential activity of Wnt/β-catenin signaling and specified distinct anterior-like (high activin/low BMP) and posterior-like (low activin/high BMP) mesodermal populations. Cardiogenic mesoderm was generated under conditions specifying anterior-like mesoderm, whereas blood-forming endothelium was generated from posterior-like mesoderm, and vessel-forming CD31+ endothelial cells were generated from all mesoderm origins. Surprisingly, inhibition of β-catenin signaling led to the highly efficient respecification of anterior-like endothelium into beating cardiomyocytes. Cardiac respecification was not observed in posterior-derived endothelial cells. Thus, activin/BMP gradients specify distinct mesodermal subpopulations that generate cell derivatives with unique angiogenic, hemogenic and cardiogenic properties that should be useful for understanding embryogenesis and developing therapeutics.

Palpant NJ1*, Pabon L1, Roberts M, Hadland B, Jones D, Jones C, Moon R, Ruzzo W, Bernstein I, Zheng Y, Murry CE. Inhibition of β-catenin signaling re-specifies anterior-like endothelium into beating human cardiomyocytes. Development 2015 Sep 15;142(18):3198-209. 1Equal first authors


*This study was performed when Nathan Palpant was at the Department of Pathology, the Centre for Cardiovascular Biology, and the Institute for Stem Cell and Regenerative Medicine, at the University of Washington School of Medicine, Seattle, USA.


© 2015. Published by The Company of Biologists Ltd.

Palpant Development 2015 cover

 




About the cover:

Human embryonic stem cells were differentiated into endocardial endothelial-like cells and seeded into a microfluidic network to create engineered microvessels. Microvessel networks show angiogenic sprouting into the surrounding collagen matrix in response to flow, as shown here by confocal microscopy for CD31 expression (red); nuclei are counterstained with DAPI (blue).