Study the impact of stress on cell identity.

The Development and Environment Interface team led by Valérie Mezger studies the impact of stress on cell identity. We aim to understand how prenatal stress perturbs neural cell fate and therefore contributes to neurodevelopmental disorders (NDDs) and study how stress-responsive molecular pathways shape normal and pathological neurodevelopment. For this, we focus on stressors of prenatal relevance (prenatal alcohol exposure or neuroinflammation, induced by infections), which are major causes of non-genetic NDDs). Using human cerebral organoids, we demonstrated that deregulation of stress-responses is also observed in monogenic NDDs and therefore have developed a transfer project with a Company and Mathematicians in deep learning which capitalizes on stress responses to build new therapeutic strategies. Valérie Mezger is also co-leader of the Preclinical Workpackage of the IHU Robert of the Child Brain (ICE).

Main techniques

We focus on prenatal stressors (alcohol exposure or infection-induced neuroinflammation), which are major causes of non-genetic neurodevelopmental disorders (NDDs) in mouse models. Regarding genetically based NDDs, we combine the use of human brain organoids with genome editing (CRISPR/Cas) to build isogenic models, coupled with multi-omics approaches in single cells (gene expression and chromatin accessibility within the same cell) and phenotyping using deep learning development through collaborations (A. Genovesio, iBENS, Paris). We also use these models in screening approaches for active molecules in collaboration with iStem (A. Benchoua).

Address :
35, rue Hélène BRION, Campus des Grands-Moulins, Université Paris Cité, 75013 PARIS

Team leader :
Valérie Mezger
Name of co-team leader :

Administrative Contact Name :


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Key words : #Neurodéveloppement# facteurs de transcription de réponse au stress#TDN d’origines génétiques et environnementales#; organoïdes cérébraux#modèles murins#approches multi-omiques en cellules-uniques#édition du génome #Neurodevelopment#stress response transcription factors#genetic and environmental neurodevelopmental disorders# brain organoids# mouse models# single-cell multi-omics approaches# genome editing