Multi-layered regulation of neuroectoderm differentiation by retinoic acid in a primitive streak-like context.
Stem Cell Reports
; 17(2): 231-244, 2022 02 08.
Article
em En
| MEDLINE
| ID: mdl-35063128
ABSTRACT
The formation of the primitive streak (PS) and the subsequent induction of neuroectoderm are hallmarks of gastrulation. Combining an in vitro reconstitution of this process based on mouse embryonic stem cells (mESCs) with a collection of knockouts in reporter mESC lines, we identified retinoic acid (RA) as a critical mediator of early neural induction triggered by TGFß or Wnt signaling inhibition. Single-cell RNA sequencing analysis captured the temporal unfolding of cell type diversification, up to the emergence of somite and neural fates. In the absence of the RA-synthesizing enzyme Aldh1a2, a sensitive RA reporter revealed a hitherto unidentified residual RA signaling that specified neural fate. Genetic evidence showed that the RA-degrading enzyme Cyp26a1 protected PS-like cells from neural induction, even in the absence of TGFß and Wnt antagonists. Overall, we characterized a multi-layered control of RA levels that regulates early neural differentiation in an in vitro PS-like system.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Diferenciação Celular
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha