Nature: research and creation of new human brain "organ like"

June 11, 2019 / BIOON / - scientists from Harvard University and the Stanley Center for psychological research of Broad Institute have made great progress in developing human brain "organ like" "Organ like" is a kind of micro three-dimensional tissue culture, which can simulate patients' own brain cells in a culture dish Their new method, published in the journal Nature, continues to grow the same types of cells in the same order as the development of the human cortex This progress may change the way researchers study neuropsychiatric diseases and test the effectiveness of drugs The genetics behind human nervous system diseases is complex, and the large-span genome is involved in the occurrence and development of diseases Research into other animal neurological diseases offers limited opportunities for discovery because the human brain is unique Photo source: nature organs provide great hope for the direct study of human diseases But so far, they have failed in a very important way "We may use our brains in different ways, but each of us has the same cell type and basic connections," explains Paola arlota, a professor of stem cell and regenerative biology at the Golub family at Harvard University and a member of the Stanley center "This consistency is crucial, with very few exceptions, and is replicated every time the human brain is formed in the womb There are only minimal differences between us in cell types and structures of the brain "So far, this has not been the case with organoids Although they do produce human brain cells, each one is unique This means that it is not easy to use them to compare the differences between diseased and normal brain tissues "Organoids have greatly improved our ability to study human brain development," Arlotta said "But until now, each cell has been a snowflake, forming its own unique combination of cell types in a way that was initially unpredictable And our research solves this problem "Based on pioneering work led by the late stem cell biologist Yoshiki sasai, the team has created quasi organs that are almost indistinguishable from each other - even if they have grown in the laboratory for more than six months In addition, under specific culture conditions, organ like organs are healthy and can develop long enough to produce a wide range of cell types, usually found in the human cerebral cortex These advances mean that brain organs can now be used as a feasible experimental system to directly study diseases in patients' tissues and compare the effects of different drugs on human brain tissues The same cells, the same way, the researchers focused on organ like parts of the cerebral cortex: the parts of the brain responsible for cognition, language, and sensation The cerebral cortex plays a key role in neuropsychiatric diseases such as autism and schizophrenia "We make organ like organisms from a variety of stem cell lines from men and women, so their genetic background is different," explains Silvia Velasco, a research scientist at Harvard University and the Broder Institute and lead author Human brain tissue grows very slowly In this study, six months later, the diameter of an organ like organ had grown to 3 mm In the largest single-cell RNA sequencing experiment to date, researchers grouped cells according to genes expressed at different stages Using the computational model of big data analysis, they compared each group of cells with the types of cells developed in the embryonic cerebral cortex "Despite the different genetic backgrounds, we found that the same cell types are formed in the same way and in the right order, most importantly in every organ," Velasco said We are really excited that this model gives us such consistency "A new way to study diseases using the methods optimized in this study, researchers can extract organ like cells from patients' stem cells, or engineering cells from cells with mutations related to specific diseases Arlota's lab is currently exploring autism, using CRISPR / cas9 gene editing technology to develop brain like organs for autism "It is now possible to compare 'control' organs with mutants we know to be disease-related This will allow us to determine more about which differences are meaningful, which cells are affected, and which molecular pathways are wrong, "Arlotta said "Having renewable organoids will help us to take specific interventions faster, as they will guide us to the specific genetic characteristics that cause the disease In the future, I think we will be able to ask more precise questions about mental illness "We have gained a remarkable understanding of many different cell types in the human brain in a very short time," said Aviv Regev, coauthor "This knowledge has laid the foundation for us to create this extremely complex organ model Overcoming the problem of repeatability has opened the door to the study of the human brain, which was considered impossible just a few years ago "Reference: Paola arlota et al Individual brain organizations reproduction form cell diversity of the human cerebellar cortex, nature (2019) Doi: 10.1038/s41586-019-1289-x