He is small though…
Scientists have grown the "right" mini-brains in a bioreactor
Daria Spasskaya, N+1
American neuroscientists told in an article in Nature (Velasco et al., Individual brain organoids reproducibly form cell diversity of the human cerebral cortex) about a new protocol for growing several types of advanced brain organoids from induced human stem cells. As shown by a large-scale analysis of gene expression in individual cells of mini-brains, within six months the cellular diversity of the human cerebral cortex is reproducibly formed as part of such organoids.
In order to study the brain in vitro, outside the human body, researchers are trying to reproduce "in vitro" the process of embryonic neurogenesis, which would result in an organ that mimics the complexity of the structure of a real brain. A few years ago, neuroscientists learned how to grow organoids containing parts that resemble different parts of the brain, including the cortex, in structure and gene expression patterns. However, such mini-brains formed rather chaotically, and due to the limited growth time, they did not have time to form all types of cells.
Researchers from Harvard and the Broad Institute (USA), led by Paola Arlotta, learned how to grow organoids within six months, not three, as before. This became possible thanks to the use of a bioreactor with a complex growth medium, the constant mixing of which made it possible to avoid hypoxia.
The authors of the protocol proposed several modifications for growing organoids that mimic the whole brain with different parts, the forebrain (cortex) and two variants of 3D cultures for the dorsal and ventral sections. All models are proposed to be grown from induced pluripotent stem cells (iPSC), that is, cells that have been artificially returned from an "adult" state (for example, skin cells) to an embryonic one.
Four types of three-dimensional models grown in a bioreactor from PGP1 cells, aged 6 months. A drawing from an article in Nature.
The researchers first grew the four mentioned modifications from the same iPSC cell line using a multicomponent growth medium. Then the result was reproduced on five different lines, thereby showing that the process of organoid formation does not depend on the genetic differences of cells.
To show that within six months all the variety of types of neurons and auxiliary cells have time to form in the "mini-brain", the authors of the work "broke down" the obtained organoids and conducted a large-scale analysis of gene expression using RNA sequencing of individual cells. In total, the scientists obtained data for 160 thousand transcriptomes of individual cells from 21 samples. The obtained expression patterns, firstly, turned out to be identical to each other for different samples, which indicates the reproducibility of the formation of "organs" in the bioreactor, which previously could not be achieved. Secondly, a comparison with the patterns of gene expression in real brains allowed us to conclude about the full cellular composition of organoids.
New models of organoids that can be grown even from the cells of a particular patient will allow us to study the differences in the work of the brain of people with various diseases, in particular, autism, the authors comment on the study. The beginning of such experiments has already been laid – for example, the authors of the experiment on growing a "full-fledged" brain organoid investigated the changes leading to the development of microcephaly. We also told how the introduction of a single mutation characteristic of Neanderthals into the genome changed the structure of neural connections in the composition of an organoid that mimics the cortex.
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