ZENITH: A Flow Cytometry Based Method for Functional Profiling Energy Metabolism with Single Cell Resolution

Abstract

Energetic metabolism (EM) reprogramming is critical for both cancer and immune response initiation. Current methods for EM monitoring are performed in bulk and do not have the sensitivity nor the resolution to dissect EM at single cell scale. We designed a novel EM profiling method called ZENITH, that provides single-cell resolution using multiparametric flow cytometry. ZENITH highlights the dichotomy among EM displayed respectively by naive, effector and memory T cells, demonstrating its ability to discriminate cell subsets on the basis on their specific metabolic status. Tumor-associated myeloid cells isolated from biopsies are also shown to display highly variable EM profiles, in ways that are not linked to their lineage nor their activation phenotype. ZENITH ability to determine complex and linked metabolic activities in discrete cell subpopulations within tissue or blood draws will contribute to the functional information needed for evaluating therapeutic responses or patient stratification.