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Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes

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 hum...

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Autores principales: Palpant, Nathan J., Pabon, Lil, Roberts, Meredith, Hadland, Brandon, Jones, Daniel, Jones, Christina, Moon, Randall T., Ruzzo, Walter L., Bernstein, Irwin, Zheng, Ying, Murry, Charles E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582173/
https://www.ncbi.nlm.nih.gov/pubmed/26153229
http://dx.doi.org/10.1242/dev.117010
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author Palpant, Nathan J.
Pabon, Lil
Roberts, Meredith
Hadland, Brandon
Jones, Daniel
Jones, Christina
Moon, Randall T.
Ruzzo, Walter L.
Bernstein, Irwin
Zheng, Ying
Murry, Charles E.
author_facet Palpant, Nathan J.
Pabon, Lil
Roberts, Meredith
Hadland, Brandon
Jones, Daniel
Jones, Christina
Moon, Randall T.
Ruzzo, Walter L.
Bernstein, Irwin
Zheng, Ying
Murry, Charles E.
author_sort Palpant, Nathan J.
collection PubMed
description 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.
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spelling pubmed-45821732015-11-04 Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes Palpant, Nathan J. Pabon, Lil Roberts, Meredith Hadland, Brandon Jones, Daniel Jones, Christina Moon, Randall T. Ruzzo, Walter L. Bernstein, Irwin Zheng, Ying Murry, Charles E. Development Stem Cells and Regeneration 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. The Company of Biologists 2015-09-15 /pmc/articles/PMC4582173/ /pubmed/26153229 http://dx.doi.org/10.1242/dev.117010 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Stem Cells and Regeneration
Palpant, Nathan J.
Pabon, Lil
Roberts, Meredith
Hadland, Brandon
Jones, Daniel
Jones, Christina
Moon, Randall T.
Ruzzo, Walter L.
Bernstein, Irwin
Zheng, Ying
Murry, Charles E.
Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
title Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
title_full Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
title_fullStr Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
title_full_unstemmed Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
title_short Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
title_sort inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes
topic Stem Cells and Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582173/
https://www.ncbi.nlm.nih.gov/pubmed/26153229
http://dx.doi.org/10.1242/dev.117010
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