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Cerebral organoids: modelling human brain development and tumorigenesis in stem cell derived 3D culture

Date: Wednesday, December 5, 2018 12:00 - 13:15
Speaker: Juergen A. Knoblich (IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Science Vienna)
Location: Mondi Seminar Room 2, Central Building
Series: Life Sciences Seminar
Host: Simon Hippenmeyer
Contact: MARR Lena

Abstract:

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. Furthermore, human cerebral organoids display stem cell properties and progenitor zone organization that show characteristics specific to humans. 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 been able to generate organoid based models for human brain cancer and demonstrated their feasibility for drug testing. Our data demonstrate an in vitro approach that recapitulates development of even this most complex organ, which can be used to gain insights into disease mechanisms.
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