“We were really excited that this model gave us such consistency.” “Despite the different genetic backgrounds, we saw that the same cell types were made in the same way, in the correct order and, most importantly, in each organoid,” said Velasco. Using computational models for big data analysis, they compared each group to the cell types that develop in the embryonic cerebral cortex. In the largest single-cell RNA sequencing experiment in brain organoids to date, the researchers grouped cells based on which genes were expressed at different stages. In this study, after six months the organoids had grown to three millimeters across. “We made organoids from multiple stem cell lines, from both male and female origins – so their genetic backgrounds were different,” explained lead author Silvia Velasco, a postdoctoral fellow at Harvard and the Broad Institute. The cerebral cortex plays a key role in neuropsychiatric diseases such as autism spectrum disorder and schizophrenia. The researchers focused on organoids of the cerebral cortex, the part of the brain responsible for cognition, language, and sensation. These advances mean that brain organoids can now be used as viable experimental systems to study diseases in patient tissues directly, and to compare different drug effects on human brain tissues. We solved that problem.”īuilding on seminal work led by the late stem cell biologist Yoshiki Sasai, the team created organoids that are virtually indistinguishable from one another – even when grown for longer than six months in the laboratory.įurthermore, under specific culture conditions the organoids were healthy and able to develop long enough to produce a broad spectrum of cell types normally found in the human cerebral cortex. “But until now, each one has been its own snowflake, making its own special mix of cell types in a way that could not have been predicted at the outset. “Organoids have dramatically advanced our ability to study the human developing brain,” said Arlotta. That means they cannot be used easily to compare differences between diseased and control brain tissues reliably.
While they do generate human brain cells, each one is unique. So far, that has not been the case with organoids. There are only the smallest differences between us, in terms of the cell types and structures in our brains.” “That consistency is crucial and, with very few exceptions, it is reproduced every time the human brain forms in the womb. “We might all use our brains differently, but each of us has the same collection of cell types and basic connections,” explained senior author Paola Arlotta, the Golub Family Professor of Stem Cell and Regenerative Biology at Harvard and a member of the Stanley Center. But so far, they have failed in one very important way. Organoids offer great promise for studying disease in humans directly. Studying neurological diseases in other animals gives limited opportunities for relevant discovery, as human brains are quite distinctive.
The genetics behind human neurological disease are complex, with large spans of the genome contributing to disease onset and progression. The advance could change the way researchers study neuropsychiatric diseases and test the effectiveness of drugs. Their new method, published in Nature, consistently grows the same types of cells, in the same order, as the developing human cerebral cortex. Scientists at Harvard University and the Broad Institute’s Stanley Center for Psychiatric Research have made a major advance in the development of human brain ‘organoids’: miniature, 3D tissue cultures that model a patient’s own brain cells in a dish. Next Generation in Biomedicine Symposium.Science Writing and Communications Internship.Stanley Center for Psychiatric Research.Genome Regulation, Cellular Circuitry and Epigenomics.Chemical Biology and Therapeutics Science.