Rubicon 2022 – Bas Lendemeijer – In vivo maturation and activity of xenografted human induced pluripotent stem cell-derived neurons

Project summary

Animal models have provided insight into fundamental features of the brain. Unfortunately, this increase in knowledge has not resulted in improved treatment for patients suffering from psychiatric disorders. The study of the human brain is hampered by a lack of availability of the primary tissue and species differences between humans and experimental animals. Induced pluripotent stem cell (iPSC)-technology provides an opportunity to address both issues, numerous protocols have been established to generate iPSC-derived neurons in vitro. Even though some protocols span several months to a year, the field has been unable to create iPSC-derived neural cells that physiologically reach a postnatal developmental age. Here, I propose a novel model in which human iPSC-derived neurons are xenografted into the brain of mouse in an attempt to expose them to physiological stimuli and reach a postnatal developmental age. Using advanced two-photon imaging-techniques the development of iPSC-derived neuronal ensembles can be monitored in vivo over extended periods of time.

The proposed imaging setup is small enough to allow the mouse to freely behave while continuously recording the activity of hundreds of iPSC-derived neurons, creating the opportunity to study how control- and patient-derived neurons respond to real-world stimuli and participate in brain circuits.