Invitado: Adrian E. Granada – Humboldt-Universität zu Berlin.
Título: Single cell cell-fate choices in response to Cisplatin.
Abstract: Cells within a single tumor display great diversity at their epigenetic, transcriptome and proteome states. These internal factors alone can generate significant phenotypic and behavioral heterogeneity and thereupon variation in response to drugs. Chemotheraputic DNA damaging agents induce tumor regression through cell cycle arrest and apoptosis. These individual cell fate choices are shaped by the distribution of cellular states across the tumor and collectively determine the overall response to therapy.
Recent studies tracking sister cells over time under DNA damage suggest that heritable features rather that stochastic differences dominate the balance of cell fate choices. Furthermore, these studies show links between cell state and the fate of cells after treatment, but the variables explored in each study (e.g. p53 signaling or circadian rhythm) explain a significant but relatively minor portion of the observed variation, suggesting our understanding of the contribution of the internal cell state to cell fate is missing important features.
To tackle this problem, we combined long term live single-cell microscopy using reporters of cell cycle phases and a rigorous analytical framework. Our approach permits us to extract cell-fate specific refractory times and cell-fate commitment timescales, identify proliferative subgroups of cells and cell-cycle states with differential sensitivity to cisplatin.