ലബോറട്ടറിയിൽ വളർത്തിയെടുത്ത നാഡീകോശങ്ങൾ ഭ്രൂണാവസ്ഥയിലെ സവിശേഷതകൾ നിലനിർത്തുന്നു: പുതിയ പഠനം

Scientists from Skoltech, together with colleagues from the Kharkevich Institute for Information Transmission Problems of the Russian Academy of Sciences, Lomonosov Moscow State University and other organizations, conducted a comparative study of the 3D genome organization in neurons derived from induced pluripotent stem cells and in neurons of the adult human brain. The authors collected and processed more than 300 3D genome maps covering 62 human samples and 34 mouse samples, including data on embryonic stem cells, induced pluripotent stem cells, neural progenitors, fetal and postmortem neurons, as well as neurons differentiated in vitro.

The work also presents five new 3D genome maps obtained by the authors. The study is published in the journal Genome Research.

Induced pluripotent stem cells are cells obtained from adult somatic cells through genetic reprogramming, which returns them to a state similar to the embryonic one. Neurons genetically identical to the donor can be derived from these cells, enabling the study of nervous system diseases under laboratory conditions. However, until now it remained unclear how closely such neurons replicate the chromatin architecture of mature adult brain neurons.

The analysis showed that neurons differentiated from induced pluripotent stem cells are closer in their chromatin properties to neuronal progenitor cells than to mature neurons. In these cells, active and inactive regions of the genome are separated more distinctly, and the boundaries of structural domains (regions where DNA interacts with itself) contain genes associated with development. At the same time, long repressive contacts, which in mature neurons suppress gene expression, are much less pronounced in lab-grown neurons.

The structural domains themselves in such neurons are smaller and more densely packed, which is characteristic of progenitor cells. In addition, they show reduced activity of frequently interacting regulatory regions that normally control gene expression.

"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," stated Ekaterina Khrameeva, scientific supervisor of the work, an associate professor at the Biomed Technologies Center of Skoltech.

"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.