Lab-grown ‘minibrains’ differ from the real thing in cell subtypes, gene expression

Science | AAAS | 1/29/2020 | Staff
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Glance at an intricately structured blob of human brain cells in a lab dish, and it’s tempting to dub it a “minibrain.” That’s the popular term for cerebral organoids, complex 3D tissues made from stem cells that are revolutionizing how researchers study neural development and conditions from autism to Zika. But the most comprehensive genetic comparison yet of cells from real brains and cerebral organoids, published today, reveals important differences between them.

Arnold Kriegstein, a neuroscientist at the University of California, San Francisco, and his colleagues first cataloged the genes turned on in individual cells from different parts of human fetal brains at 6 to 22 weeks of gestation. They then compared these patterns of gene expression to those of cells from cerebral organoids created using several previously published methods.

Categories - Brain - Cells—like - Neurons - Cells

When it came to broad categories of brain cells—like neurons and nonneuronal cells called glia—the gene expression generally matched up. But when the researchers examined more precise subtypes of cells—a subset cells known as outer radial glia, for example—the comparisons started to break down. The organoid cells weren’t reliably maturing and expressing the specific combinations of genes that distinguish one subtype of cell from another.

That’s a potential limitation for studies that use organoids to model disease. Many such studies “reprogram” cells from a person with a disease into stem cells that can form an organoid. But nervous system diseases are highly cell-type specific, says Kriegstein, making it hard to draw conclusions about the disease if your lab-grown model doesn’t contain the exact cell type affected in the brain.

Cells - Subtypes - Way - Signatures - Regions

Though the organoid cells didn’t generally mature into precise subtypes, they did become specialized in another way: They took on genetic signatures that correspond to different regions of the brain. But those identities came on...
(Excerpt) Read more at: Science | AAAS
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