ERK5 promotes autocrine expression to sustain mitogenic balance for cell fate specification in human pluripotent stem cells.
Stem Cell Reports
; 19(9): 1320-1335, 2024 Sep 10.
Article
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| MEDLINE
| ID: mdl-39151429
ABSTRACT
The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation. ERK5 inhibition leads to erroneous cell fate specification in all lineages even under lineage-specific induction. hPSCs can self-renew under ERK5 inhibition in the presence of fibroblast growth factor 2 (FGF2) and transforming growth factor ß (TGF-ß), although NANOG expression is partially suppressed. Further analysis demonstrates that ERK5 promotes the expression of autocrine factors such as NODAL, FGF8, and WNT3. The addition of NODAL protein rescues NANOG expression and differentiation phenotypes under ERK5 inhibition. We demonstrate that constitutively active ERK5 pathway allows self-renewal even without essential growth factors FGF2 and TGF-ß. This study highlights the essential contribution of autocrine pathways to proper maintenance and differentiation.
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Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Comunicación Autocrina
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Células Madre Pluripotentes
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Proteína Quinasa 7 Activada por Mitógenos
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Proteína Homeótica Nanog
Límite:
Humans
Idioma:
En
Revista:
Stem Cell Reports
Año:
2024
Tipo del documento:
Article
País de afiliación:
China