Pten-mediated Gsk3ß modulates the naïve pluripotency maintenance in embryonic stem cells.
Cell Death Dis
; 11(2): 107, 2020 02 07.
Article
en En
| MEDLINE
| ID: mdl-32034125
ABSTRACT
Mouse embryonic stem cells (ESCs) are isolated from the inner cell mass of blastocysts, and they exist in different states of pluripotency-naïve and primed states. Pten is a well-known tumor suppressor. Here, we generated Pten-/- mouse ESCs with the CRISPR-Cas9 system and verified that Pten-/- ESCs maintained naïve pluripotency by blocking Gsk3ß activity. Serum/LIF and 2i (MAPK and GSK3 inhibitors) conditions are commonly used for ESC maintenance. We show that the Pten-inhibitor SF1670 contributed to sustaining mouse ESCs and that Pten activation by the S380A, T382A, and T383A mutations (Pten-A3) suppressed the pluripotency of ESCs. The in vivo teratoma formation ability of SF1670-treated ESCs increased, while the Pten-A3 mutations suppressed teratoma formation. Furthermore, the embryoid bodies derived from Pten-deficient ESCs or SF1670-treated wild-type ESCs showed greater expression of ectoderm and pluripotency markers. These results suggest that Pten-mediated Gsk3ß modulates the naïve pluripotency of ESCs and that Pten ablation regulates the lineage-specific differentiation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Linaje de la Célula
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Fosfohidrolasa PTEN
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Células Madre Embrionarias de Ratones
/
Glucógeno Sintasa Quinasa 3 beta
Límite:
Animals
Idioma:
En
Revista:
Cell Death Dis
Año:
2020
Tipo del documento:
Article
País de afiliación:
China