Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES.
Nat Commun
; 9(1): 440, 2018 01 30.
Article
em En
| MEDLINE
| ID: mdl-29382828
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas com Domínio T
/
Células-Tronco Pluripotentes
/
Técnicas de Reprogramação Celular
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article