Endothelial cell signature in muscle stem cells validated by VEGFA-FLT1-AKT1 axis promoting survival of muscle stem cell.
Elife
; 132024 Jun 06.
Article
en En
| MEDLINE
| ID: mdl-38842166
ABSTRACT
Endothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs; satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here, we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNA-seq (scRNA-seq) to show that MuSCs express low levels of canonical EC markers in mice. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Supervivencia Celular
/
Receptor 1 de Factores de Crecimiento Endotelial Vascular
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Células Endoteliales
/
Factor A de Crecimiento Endotelial Vascular
/
Proteínas Proto-Oncogénicas c-akt
Límite:
Animals
Idioma:
En
Revista:
Elife
/
ELife (Cambridge)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos