🧠 Scientists from Skoltech, the Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Lomonosov Moscow State University, and other organizations compared the 3D genome organization in lab-grown neurons and in neurons of the adult human brain. To study brain diseases, scientists grow neurons in the laboratory. They are genetically identical to the donor, and experiments can be conducted on them that cannot be done on humans. But the question remained open: how closely do lab-grown neurons resemble real adult human neurons? It turned out that lab-grown neurons never truly mature: in their structure, they are closer to progenitor cells, from which real neurons only develop. "Our results show that neurons grown from induced pluripotent stem cells do not reach the mature chromatin architecture characteristic of the adult brain. They retain features typical for early stages of development, which limits their use for modeling diseases with late onset, such as neurodegenerative ones. At the same time, these same immature properties make them suitable for studying the development of the nervous system and regulatory mechanisms critical at early stages of ontogenesis,” commented Ekaterina Khrameeva, scientific supervisor of the work, an associate professor at the Biomed Technologies Center of Skoltech. The researchers collected and processed more than 300 3D genome maps covering 62 human samples and 34 mouse samples, and also presented five new maps obtained by the authors. The database is available to the research community — it allows for systematic comparison of differentiated neurons with postmortem neurons and progenitor cells. “We created a database of 3D genome maps of human and mouse neuronal cells that is available to the research community. This allowed us to systematically compare, for the first time, the 3D organization of the genome of differentiated neurons, comparing them both with postmortem neurons and with progenitor cells. We showed that at each level, differentiated neurons differ from mature ones and retain the profile of progenitor cells. These conclusions give researchers practical criteria for choosing a model depending on the task at hand: for some questions differentiated neurons are suitable, for others they are not,” noted Diana Zagirova, first author of the work, a junior research scientist at the Biomed Technologies Center of Skoltech, and an alumna of Skoltech’s MSc program in Life Sciences. The results were published in the Genome Research journal. Skoltech is part of the VEB.RF group.