リプログラミング技術を用いた脳発生・神経疾患研究

抄録

The ultimate goals of neuroscience are to understand human brain structures and functions, and to utilize them to overcome neurological disorders. The research on the human brain had been limited to non-invasive MRI or PET studies, pathological analysis with postmortem brains or in silico genomic analyses. Although animal or cellular models had been developed for investigating neurological disorders as alternatives to living human brain tissues, many of them did not represent correct human pathological phenotypes. In these circumstances, emergence of iPSCs and organoid culture systems provides us a novel way to investigate the development and dysfunction of the human brain tissues in vitro. We developed self-organizing 3D organoid culture of iPSCs for construction of human brain tissues. Combining 3D brain organoid cultures of human PSCs, 4D imaging and image analysis, we establish efficient methods to faithfully recapitulate and to quantitatively analyze the ontogenetic formation of human brain tissues. We induce degeneration of the formed tissues to construct human neurological disease models. We further explore the ways to prevent or restore the degeneration for clinical treatment and drug discovery.

The platform based on the techniques for iPSC generation and self-organizing 3D culture will become a powerful tool for investigating human brain development and neurological diseases.