Research

Astrocytes represent the most abundant cell types in the central nervous system and play essential role in nearly all aspects of brain function, including sustaining neuronal metabolism and synaptogenesis, as well as recycling neurotransmitters and supporting neuronal survival. Given their pleiotropic functions and their close relationship with the surrounding neurons, it is not surprising that perturbations of astrocyte development have been associated with a variety of complex neurodevelopmental disorders, including Alzheimer and Huntington diseases, and frontotemporal dementia.

 

Although neurons have been accepted since long a very diverse population, astrocytes are generally considered as a relatively homogeneous cell type. However, the idea that cortical astrocytes could constitute also a various population at morphological, molecular and functional level, has been increasingly entertained in the last decade. Despite these recent advances regarding heterogeneity of adult cortical astrocytes, little is known about the exact molecular mechanisms underlying the acquisition of specific astrocytic subtype during development. 

 

Our work tries to understand how cell intrinsic (i.e., genes) and extrinsic (i.e., extracellular environment) mechanisms contribute to shape astrocytes diversity during development and elucidate how this diversity changes upon brain injury or disease. This represents a crucial step for gaining critical insights into how reported developmental abnormalities in these cells potentially lead to astrocyte-related diseases, and on the other hand how these cells represent a potential therapeutic target.

 

The approaches we use to address these questions include in utero electroporation, transplantation, in vivo reprogramming, combined with high-throughput single-cell RNA sequencing, genetic barcoding and video time-laps.