Cerebral organoids: modelling human brain development and tumorigenesis in stem cell derived 3D culture
Pr Jürgen KNOBLICH
IMBA Institute of Molecular Biotechnology, Vienna Biocenter, Autriche
vendredi 12 janvier 2018 - 11h00
- Auditorium, IGBMC
The human brain is unique in size and complexity, but also the source of some of the most devastating human diseases. While many of these disorders have been successfully studied in model organisms, recent experiments have emphasized unique features that can not easily be modeled in animals. We have therefore developed a 3D organoid culture system derived from human pluripotent stem cells that recapitulates many aspects of human brain development. These cerebral organoids are capable of generating several brain regions including a well-organized cerebral cortex. With intriguing precision, they recapitulate key brain morphogenetic events like the formation of distinct progenitor and differentiation zones, the generation of neuronal subclasses with distinct layer identities and the establishment of coordinated neuronal activity. We have used patient specific iPS cells to model microcephaly, a human neurodevelopmental disorder that has been difficult to recapitulate in mice. This approach reveals premature neuronal differentiation with loss of the microcephaly protein CDK5RAP2, a defect that could explain the disease phenotype. More recently, we have developed organoid based models for long distance interneuron migration between distinct areas of the human brain which we are using for modeling neuropsychiatric disorders. Our data describe an in vitro approach that recapitulates development of even the most complex organ and can be used to gain insights into disease mechanisms.