Mapping human brain development
Researchers from the group of Barbara Treutlein are growing human brain-like tissue from stem cells and are then mapping the cell types that occur in different brain regions and the genes that regulate their development.
The human brain is probably the most complex organ in the entire living world and has long been an object of fascination for researchers. However, studying the brain, and especially the genes and molecular switches that regulate and direct its development, is no easy task.
To date, scientists have proceeded using animal models, primarily mice, but their findings cannot be transferred directly to humans. A mouse’s brain is structured differently and lacks the furrowed surface typical of the human brain. Cell cultures have thus far been of limited value in this field, as cells tend to spread over a large area when grown on a culture dish; this does not correspond to the natural three-dimensional structure of the brain.
Mapping molecular fingerprints
A group of researchers led by Barbara Treutlein, ETH Professor at the Department of Biosystems Science and Engineering in Basel, has now taken a new approach to studying the development of the human brain: they are growing and using organoids – millimetre-sized three-dimensional tissues that can be grown from what are known as pluripotent stem cells.
Provided these stem cells receive the right stimulus, researchers can program them to become any kind of cell present in the body, including neurons. When the stem cells are aggregated into a small ball of tissue and then exposed to the appropriate stimulus, they can even self-organise and form a three-dimensional brain organoid with a complex tissue architecture.
In a new study just published in Nature, Treutlein and her colleagues have now studied thousands of individual cells within a brain organoid at various points in time and in great detail. Their goal was to characterise the cells in molecular-genetic terms: in other words, the totality of all gene transcripts (transcriptome) as a measure of gene expression, but also the accessibility of the genome as a measure of regulatory activity. They have managed to represent this data as a kind of map showing the molecular fingerprint of each cell within the organoid.
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Human Cell Atlas
The research and mapping of brain organoids is embedded in the Human Developmental Cell Atlas; this, in turn, is part of the Human Cell Atlas. The external pageHuman Cell Atlas is an attempt by researchers worldwide both to map all cell types in the human body and to compile data on which genes are active in which cells at which times as well as on which genes might be involved in diseases. The head of the Human Cell Atlas project is Aviv Regev, a biology professor at MIT; she received an honorary doctorate from ETH Zurich in 2021. ETH Professor Barbara Treutlein is co-coordinating the Organoid Cell Atlas subsection, which aims to map all the cell stages that can be produced in cell culture and then to compare them with the original cells of the human body.
Find research article in Nature:
Fleck, JS, SMJ Jansen, D Wollny, M Seimiya, F Zenk, M Santel, Z He, JG Camp, and B Treutlein (2022) external pageInferring and perturbing cell fate regulomes in human brain organoids. Nature, online published 5. October. Doi: 10.1038/s41586-022-05279-8
Learn about the Quantitative Developmental Biology lab led by Barbara Treutlein.