Intracellular Ca2+ Homeostasis and Nuclear Export Mediate Exit from Naive Pluripotency.
Cell Stem Cell
; 25(2): 210-224.e6, 2019 08 01.
Article
em En
| MEDLINE
| ID: mdl-31104942
ABSTRACT
Progression through states of pluripotency is required for cells in early mammalian embryos to transition away from heightened self-renewal and toward competency for lineage specification. Here, we use a CRISPR mutagenesis screen in mouse embryonic stem cells (ESCs) to identify unexpected roles for nuclear export and intracellular Ca2+ homeostasis during the exit out of the naive state of pluripotency. Mutation of a plasma membrane Ca2+ pump encoded by Atp2b1 increased intracellular Ca2+ such that it overcame effects of intracellular Ca2+ reduction, which is required for naive exit. Persistent self-renewal of ESCs was supported both in Atp2b1-/-Tcf7l1-/- double-knockout ESCs passaged in defined media alone (no LIF or inhibitors) and in wild-type cells passaged in media containing only calcitonin and a GSK3 inhibitor. These new findings suggest a central role for intracellular Ca2+ in safeguarding naive pluripotency.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinalização do Cálcio
/
Células-Tronco Pluripotentes
/
Espaço Intracelular
/
ATPases Transportadoras de Cálcio da Membrana Plasmática
/
Proteína 1 Semelhante ao Fator 7 de Transcrição
/
Células-Tronco Embrionárias Murinas
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article