Assembling human brain organoids

SP Paşca - Science, 2019 - science.org
Science, 2019science.org
Brain development is a remarkable self-organization process in which cells proliferate,
differentiate, migrate, and wire to form functional neural circuits. In humans, this process
takes place over a long fetal phase and continues into the postnatal period, but it is largely
inaccessible for direct, functional investigation at a cellular level. Therefore, the features that
make the human central nervous system unique and the sequence of molecular and cellular
events underlying brain disorders remain largely uncharted. Human pluripotent stem (hPS) …
Brain development is a remarkable self-organization process in which cells proliferate, differentiate, migrate, and wire to form functional neural circuits. In humans, this process takes place over a long fetal phase and continues into the postnatal period, but it is largely inaccessible for direct, functional investigation at a cellular level. Therefore, the features that make the human central nervous system unique and the sequence of molecular and cellular events underlying brain disorders remain largely uncharted. Human pluripotent stem (hPS) cells, including those obtained by reprogramming somatic cells, have the ability to self-organize and differentiate when grown in three-dimensional (3D) aggregates rather than in direct contact with a flat plastic surface (1). Such 3D neural cultures, also known as organoids and organ spheroids, recapitulate many aspects of human brain development in vitro (1) and have the potential to accelerate progress in human neurobiology. Here, I discuss the emerging approaches to produce brain assembloids—the next generation of brain organoids that combine multiple cell lineages in 3D. These cultures can be used to model interactions between various brain regions in vitro, and ultimately may be applied to understand the assembly of neural circuits and to capture complex cell-cell interactions in the brain.
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