Speaker
Description
Brain organoids represent the 3D tissues that recapitulate the structure and function of the developing human brain. Much efforts have been made to advance the regionalization and to utilize the brain organoids to study human diseases. We developed region-specific cortical organoids and used them to study Rett syndrome. Since neuroectoderm differentiation of the human embryonic stem cells (hESCs) is an essential first step in brain organoid formation, the majority of cells in brain organoids are of the neuroectoderm origin. However, the cells that comprise the blood vessel in brain, and the residential immune cells in brain are from the mesoderm. In order to implement the mesoderm cells in brain organoids, we genetically engineered the hESCs to express the transcription factors that facilitate the formation of vascular-like structure and microglia-like cells. The vascular-like structures highly improved the quality of the brain organoids, dramatically decreasing the cell death, and increasing the neural maturation. The microglia-like cells demonstrated the innate immune function such as phagocytosis. Overall, our engineered brain organoids provide the essential mesoderm-derived cells in neuroectoderm-oriented brain organoids that play critical roles in brain function.
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