Reprogramming Roadblocks Are System Dependent.
Stem Cell Reports
; 5(3): 350-64, 2015 Sep 08.
Article
em En
| MEDLINE
| ID: mdl-26278041
ABSTRACT
Since the first generation of induced pluripotent stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here, we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights mesenchymal-to-epithelial transition (MET) as a roadblock but also faces more severe difficulties to attain a pluripotent state even post-MET. In contrast, more efficient cassettes can reprogram both wild-type and Nanog(-/-) fibroblasts with comparable efficiencies, routes, and kinetics, unlike the less efficient reprogramming systems. Moreover, we attribute a previously reported variation in the N terminus of KLF4 as a dominant factor underlying these critical differences. Our data establish that some reprogramming roadblocks are system dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Reprogramação Celular
/
Células-Tronco Pluripotentes Induzidas
/
Transição Epitelial-Mesenquimal
/
Fibroblastos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido