Reversing the Epigenetic and Transcriptional Imprints of Glucose-Induced Cellular Memory

About
Vascular dysfunction is a key contributor to diabetes-related complications, often driven by the long-lasting effects of transient hyperglycaemia, a phenomenon known as metabolic memory. To investigate its molecular basis, we performed transcriptional and epigenetic profiling in human endothelial cells exposed to transient high glucose (HG) detecting persistent gene expression and chromatin changes that remain after glucose normalization. Chromatin accessibility and histone modification analyses revealed that these enduring effects are enriched in non-promoter regions, particularly enhancers, which retain activation-associated histone marks. Integrative chromatin state modelling identified both de novo and stable transitions associated with cis-regulatory elements, indicating a central role for enhancers in sustaining transcriptional changes. Notably, activation of the NRF2 pathway using sulforaphane reversed many of the transcriptional and epigenetic alterations induced by transient HG. These findings highlight enhancers as key mediators of chromatin-based metabolic memory and suggest that targeting epigenetic regulators may provide a therapeutic strategy to mitigate long-term vascular damage in diabetes.

Bio
Dr. Julián Valdés earned his undergraduate and PhD degrees in Biomedical Sciences from UNAM (Mexico City), where he conducted pioneering research finding a new family of cholesterol transport proteins (PhD, 2012). He completed his postdoctoral training at the Black Family Stem Cell Institute, Mount Sinai Hospital (NYC), specializing in epigenetics and stem cell differentiation (2012–2017). As a recipient of the prestigious PEW Latin American Fellowship, he received advanced training in molecular biology and bioinformatics. Since 2018, he has been Principal Investigator at the Institute of Cellular Physiology (UNAM), where he leads the “Epigenetics and Environment” lab. His research explores how environmental factors influence the epigenome and gene expression in health and disease, addressing conditions such as high glucose exposure, HIV-associated inflammation, and behavioural changes in animal neurons. 
 

Hosted by Miguel Fidalgo. Stem Cells and Human Diseases Group, CiMUS

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