Organoid models of human brain development need improving if they are to faithfully model this early stage of life, a Nature study suggests.
Cortical organoids are lab-grown, three-dimensional, self-assembling balls of cells that resemble the developing human brain. These models are increasingly used to study brain development; however, it remains unclear how accurate they are, because there have been limited comparisons of the catalogue of cells and molecules that exist in the developing brain and in these models. To address this issue, Arnold Kriegstein and colleagues recorded gene expression profiles from about 200,000 individual cells taken from the developing human cortex, and then used them as a reference list to measure the veracity of organoid cultures.
There were some important differences. Cells in the human brain follow distinct trajectories during development, producing a wide and diverse pool of cellular subtypes, but organoid cultures tend to produce less mature cell types. Although human brain cells have region-specific signatures that depend on their position within the cortex, this spatial organisation is also lacking in organoids. Many different types of organoids can be grown, so the authors hope that their study and the catalogues they provide will help others to gauge the appropriateness of their tissue culture systems.
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