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Delineating neuronal development

Although neurodegenerative disorders are increasing in incidence, therapeutic options are limited. In this context, a European project developed a method for deriving and identifying functional neurons in culture.
Delineating neuronal development
Many neurological disorders present with loss of neurons, emphasising the need for novel treatments capable of neuronal function compensation. For this purpose, intensive fundamental research on the biological mechanisms of these disorders is needed to discover and validate pharmacological treatments.

Clinical trials have demonstrated the feasibility of stem cell-based therapy in the human brain. However, this approach cannot completely stop the progression of disease possibly due to low engraftment of the administered cells. Human neural progenitors develop into electrophysiologically mature neurons at variable rates, providing significant cellular heterogeneity.

The scope of the EU-funded HND (Mechanisms of human neuronal development and functional integration in neural network) project was to study the key mechanisms of human neuronal development. By doing so, they wished to decipher how human neural progenitors functionally integrate into neural networks.

Using cell-reprogramming technologies, HND scientists developed experimental models based on induced pluripotent stem cells and studied their electrophysiological activity, morphology and transcriptome. They defined five electrophysiological types of neurons and discovered strong correlations between action potential physiology, synaptic activity, dendritic complexity and gene expression.

RNA sequencing analysis at the single cell level revealed genes that are expressed specifically in electrophysiologically mature human neurons. This molecular signature helped scientists identify and isolate functional neurons.

Taken together, the HND project succeeded at the large-scale analysis of functional neurons based on a specific molecular profile. Given that methods for the identification of mature, functional neurons were lacking, the HND approach will undoubtedly facilitate the studying of the biological mechanisms underlying neurological pathologies and validate pharmacological treatments, as well as restorative cell therapies.

Related information


Neurodegenerative disorders, neurons, culture, neural progenitors, induced pluripotent stem cells
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