Individual Cells Can Resolve Variations in Stimulus Intensity along the IGF-PI3K-AKT Signaling Axis.
Cell Syst
; 9(6): 580-588.e4, 2019 12 18.
Article
em En
| MEDLINE
| ID: mdl-31838146
ABSTRACT
Cells sense and respond to signals in their local environment by activating signaling cascades that lead to phenotypic changes. Differences in these signals can be discriminated at the population level; however, single cells have been thought to be limited in their capacity to distinguish ligand doses due to signaling noise. We describe here the rational development of a genetically encoded FoxO1 sensor, which serves as a down-stream readout of insulin growth factor-phosphatidylinositol 3-kinase IGF-PI3K-AKT signaling pathway activity. With this reporter, we tracked individual cell responses to multiple IGF-I doses, pathway inhibitors, and repeated treatments. We observed that individual cells can discriminate multiple IGF-I doses, and these responses are sustained over time, are reproducible at the single-cell level, and display cell-to-cell heterogeneity. These studies imply that cell-to-cell variation in signaling responses is biologically meaningful and support the endeavor to elucidate mechanisms of cell signaling at the level of the individual cell.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Análise de Célula Única
Limite:
Humans
Idioma:
En
Revista:
Cell Syst
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos