CV Science

Tristan Bouschet Chargé de recherche Inserm classe Normale, PhD in Neurosciences

Course and current status

Since 2009 : Researcher at the Institute of Functional Genomics -IGF-

                   INSERM U1191, CNRS UMR 5203, Montpellier, France

                   Role of Imprinted Genes in Cerebral Cortex Development

2006-2009:  Post-doc in Pierre Vanderhaeghen's lab

                   Free University of Brussels, Belgium

                   Generation of Cerebral Cortex from Embryonic Stem Cells

2002-2006:    Post-doc in Jeremy Henley's lab

                     MRC Centre for Synaptic Plasticty, Bristol, UK

                     Trafic of the Calcium Sensing Receptor

2002:             PhD in Neurosciences

                     CCIPE, Montpellier

                     Signaling by the Neurotrophic peptide PACAP

Scientific summary

Neurodegenerative diseases, including those affecting the cerebral cortex, are major societal concerns. There is no neurogenesis in the adult cortex to compensate for neuronal loss caused by disease or injury. One strategy for cortical diseases is cell therapy, whereby cortical-like neurons generated in vitro are gratfed to replace the damaged neurons. 

When postdoc in Pierre Vanderhaeghen's lab, I was involved in setting up an in vitro corticogenesis system starting from pluripotent mouse embryonic stem cells (ESCs). This system opened new perspectives in the field as we showed that the cellular complexity of the cortex can be faithfully recapitulated in vitro. We further showed that cortical-like cells can be successfully grafted in vivo. Thus, in vitro corticogenesis from ESCs is a model to understand the mechanisms of normal and deficient corticogenesis but it may also provide cells for cortical therapy at term.

I currently work in Laurent Journot's lab, which is interested in the function of imprinted genes (IGs). IGs are monoallelically expressed and the expressed allele is selected according to its parental origin. For certain IGs, only the maternal copy is expressed and for other IGs, it is only the paternal allele that is expressed. Since only one copy is expressed, IGs are particularly vulnerable and can be seen as a hotspot for numerous diseases. Indeed, inappropiate levels of certain IGs cause brain diseases such as Angelman disease and possibly autism(s).

During recent years, we have found that many IGs are expressed both in the cortex generated in vivo and in the cortex generated in vitro from ESCs. As it seemed important that cortical neurons generated in vitro resemble as much as possible to the in vivo situation, we determined to which extent the epigenetic mechanisms that are crucial for cortex development and function, such as imprinting, are recapitulated by in vitro corticogenesis. We found that in vitro corticogenesis from ESCs recapitulates quite well the imprinting status of the in vivo cortex. This suggests that this type of epigenetic signature is quite well reproduced in vitro. It also suggests that this model could be used to define the poorly identified role(s) of IGs during normal and pathological brain development (Bouschet et al., Cerebral cortex, 2017).

Besides, we have estimated the therapeutic potential of parthenogenetic (Pg) ESCs. Pg-ESCs have two maternal genomes and they can be more easily selected for histocompatibility than normal biparental (Bp) ESC lines. However, the application of Pg-ESCs to cortical therapy was unknown and their parental imprinting could have been incompatible with future therapies. We observed that mouse Pg-ESCs had a surprising 'normal', biparental-like, expression of imprinted genes. In addition, in vitro, Pg-ESCs generated cortical-like progenitors and electrophysiologically active neurons. In vivo, transplanted Pg-ESC derivatives integrated into the injured adult cortex. Collectively, this supports the utility of Pg-ESCs for neocortex repair (Varrault et al., Stem cells, 2018).

Finally, we currently work on the role of genomic imprintring and imprinted genes in normal and pathological cortex development and we try to improve cortex from ESCs as a therapeutic tool.