RESUMEN
Advances in single-cell technologies have highlighted the prevalence and biological significance of cellular heterogeneity. A critical question researchers face is how to design experiments that faithfully capture the true range of heterogeneity from samples of cellular populations. Here we develop a data-driven approach, illustrated in the context of image data, that estimates the sampling depth required for prospective investigations of single-cell heterogeneity from an existing collection of samples.
Asunto(s)
Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Análisis de la Célula Individual/métodos , Biomarcadores de Tumor , Técnicas de Cultivo de Célula , Línea Celular , Regulación Neoplásica de la Expresión Génica , HumanosRESUMEN
Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.