Invited speaker:

Rafael ARGÜELLO

Centre d´Immunologie de Marseille Luminy, Marseille, France

Abstract:

Immunological memory is built on cells that can sense, store, and recall metabolic experience. yet, while metabolism writes cues into the epigenome and epigenetic states, in turn, gate metabolic plasticity, we still lack practical ways to read both layers in the very same cells across complex human samples. This talk will trace the mechanistic links between nutrient use, cofactor availability (ATP, NADH, Acetyl-coa), and chromatin regulation, highlighting how these fluxes tune histone modifications and transcriptional poise during the epigenetic reprogramming, and the formation and persistence of memory in immune cells.
I will introduce Epic-SCENITH, an extension of SCENITHTM that functionally profiles pathway dependencies alongside epigenetic programs at single-cell resolution. By coupling inhibitor-based metabolic fingerprinting with multiparameter readouts compatible with spectral flow, Epic-SCENITH connects functional bioenergetic wiring to chromatin states and surface phenotype in one assay. I will share our results in a metabolic reprogramming model. This integrated view reveals how glycolytic stress, mitochondrial capacity, and substrate flexibility shape chromatin remodelling differentiation, is a general mechanism that can be implicated longevity, innate immune memory and recall responses.
Together, these advances close a long-standing methodological gap and open a path to rationally engineer durable immunity or to prevent the stablishment of inhibitory programs. I will share our latest results and our framework for linking metabolism to the epigenome in a low number of fixed sorted primary human cells, and with use cases where Epic-SCENITH resolves otherwise hidden heterogeneity that matters for vaccines, infection, and cancer immunotherapy.

Read more here.