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Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES
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Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES
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Journal Article
Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES
2018
Overview
Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart—yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells. Dose-dependent
EOMES
induction alone can fully replace a cocktail of signaling molecules otherwise essential for the specification of cardiogenic mesoderm. Highly efficient cardiomyocyte programming by EOMES mechanistically involves autocrine activation of canonical WNT signaling via the WNT3 ligand, which necessitates a shutdown of this axis at a subsequent stage. Our findings provide insights into human germ layer induction and bear biotechnological potential for the robust production of cardiomyocytes from engineered stem cells.
The T-box transcription factor eomesodermin (EOMES) acts both in endoderm specification as well as heart development, suggesting context-specific function. Here, the authors show that dose-controlled EOMES induction is sufficient for cardiogenic programming of human pluripotent stem cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Cell Differentiation - drug effects
/ Cellular Reprogramming Techniques - methods
/ Dose-Response Relationship, Drug
/ Doxycycline - administration & dosage
/ Embryos
/ Endoderm
/ Gene Expression Regulation, Developmental
/ Heart
/ Human Embryonic Stem Cells - cytology
/ Humanities and Social Sciences
/ Humans
/ Mesoderm
/ Myocytes, Cardiac - cytology
/ Myocytes, Cardiac - physiology
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - drug effects
/ Science
/ T-Box Domain Proteins - genetics
