Axis 1: Genomics, human cells, reprogramming and neuro-organoids

The nervous system is characterized by an extraordinary cellular diversity that underlies the architecture of our brain and the complexity of our behavior. Understanding this diversity, its formation, its mapping and its role in the normal and pathological functioning of the nervous system is a major challenge to understand and treat. To study the nervous system, recent revolutions have taken place in the field of functional genomics combined with technologies that allow the in vitro generation of neural cells and neural organoids mimicking the functioning of an entire region of the human nervous system.

Functional genomics opens the possibility to characterize and map the different subtypes of cells, their developmental trajectories, their responses to environmental changes and to target them for therapeutic purposes (gene therapy, pharmacology).

For example, the power of these approaches was recently illustrated by the partial restoration of vision in a blind patient by gene therapy.

However, there are important differences between the human nervous system and animal models. The latter do not always model certain disease symptoms. Thus, treatments that are effective in these models are sometimes ineffective in humans. Complementary human experimental models are therefore necessary. The in vitro differentiation of human induced pluripotent stem cells (iPSCs) into neural cells or neural organoids, which at the time of development and function of different brain regions, are on the way to revolutionize fundamental, clinical and industrial research in neuroscience. Indeed, iPSCs can be generated from any individual, including patients suffering from neurological disorders. Their in vitro differentiation into cortex, retina, inner ear, spinal cord... allows experimental studies, on human models, of the development and functioning of these regions in normal or pathological context. These preclinical models are compatible with large-scale toxicology, gene therapy or chemical therapy tests.

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