Human stem cell model of neural crest cell differentiation reveals a requirement of SF3B4 in survival, maintenance, and differentiation.
bioRxiv
; 2024 May 02.
Article
en En
| MEDLINE
| ID: mdl-38328054
ABSTRACT
In vitro modeling is a powerful approach to investigate the pathomechanisms driving human congenital conditions. Here we use human embryonic stem cells (hESCs) to model Nager and Rodriguez syndromes, two craniofacial conditions characterized by hypoplastic neural crest-derived craniofacial bones, caused by pathogenic variants of SF3B4, a core component of the spliceosome. We observed that siRNA-mediated knockdown of SF3B4 interferes with the production of hESC-derived neural crest cells, as seen by a marked reduction in neural crest gene expression. This phenotype is associated with an increase in neural crest cell apoptosis and premature neuronal differentiation. Altogether these results point at a role of SF3B4 in neural crest cell survival, maintenance, and differentiation. We propose that the dysregulation of these processes may contribute to Nager/Rodriguez syndrome associated craniofacial defects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
BioRxiv
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos