Science magazine looks at a mini-brain in a mini-jar – a cluster of stem cells coaxed into forming an “organoid,” a clump of cells that start taking on the functions of an organ. In this case, brain cells left to develop for a few months start undergoing the same kinds of changes as a newborn’s brain:
Things that, before I saw this paper, I would have said you can’t do with organoids … actually, maybe you can,” says Madeline Lancaster, a developmental geneticist at the Medical Research Council’s Laboratory of Molecular Biology. For example, Lancaster wasn’t optimistic about using organoids to study schizophrenia, which is suspected to emerge in the brain after birth, once neural communication becomes more complex. But she now wonders whether cells from a person with this disorder—once “reprogrammed” to a primitive, stem cell state and coaxed to mature within a brain organoid—could reveal important cellular differences underlying the condition.
Stanford University neurobiologist Sergiu Pașca has been making brain organoids for about 10 years, and his team has learned that some of these tissue blobs can thrive in a dish for years. In the new study, they teamed up with neurogeneticist Daniel Geschwind and colleagues at the University of California, Los Angeles (UCLA), to analyze how the blobs changed over their life spans.
The researchers exposed human stem cells to a specific set of growth-promoting nutrients to create spherical organoids containing neurons and other cell types found in the outer layers of the brain. They periodically removed cells to sequence their RNA, which indicates which genes are active in making proteins. Then they compared this gene expression with a database of RNA from cells of human brains of different ages. They noticed that when an organoid reached 250 to 300 days old—roughly 9 months—its gene expression shifted to more closely resemble that of cells from human brains soon after birth.
Pașca’s team also looked at the expression of genes associated with brain disorders, including autism, schizophrenia, epilepsy, and Alzheimer’s disease. The scientists identified clusters of these genes whose activity rose and fell in step, reaching their peak expression at the same time. The crests could indicate when those genes are most relevant to brain development—and at what time point an organoid might be most useful for modeling a given disorder.
You can read their research here, in Nature Neuroscience.