Research consortium produces human cell atlas

Researchers are now mapping all human cells based on the genome. For this cell atlas, three teams have now analyzed more than 500 cell types across 33 tissues in one big step and summarized them in rough maps. The teams present the work in the journal “Science”. Another team analyzed cells from embryos.

With the human cell atlas, it is possible to see in which tissues there are points of attack for corona or flu viruses, says a study leader, Sarah Teichmann from the British Wellcome Sanger Institute. She is co-founder of the Human Cell Atlas (HCA) project, which started in 2016 and involves more than 2000 researchers worldwide.

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Cross-organ perspective on cell biology

“The atlas tells us which cells have a door open for which viruses,” says Teichmann. Her team published in March 2020 that there are receptors for Sars-Cov-2 in the nose and thus demonstrated how important masks are. In addition, the researchers have shown that corona viruses also penetrate certain mucous membrane cells in the mouth and are thus ejected when speaking. “The cell atlas is like a guidebook that shows which receptor is located where.” This is also important for the development of drugs.

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The work on the cell atlas has been going on for years, but so far mainly individual cells, tissues or organs have been catalogued, explains Teichmann, who is also research director at the British University of Cambridge. With the cell maps presented in “Science”. show across organs how cells work together.

Reference work for all cells

“In the immune system, we have now learned which T cells are present in which tissues and thus created a kind of GPS,” says Teichmann. T cells form different receptors in the spleen than in other organs. In addition, the analysis techniques have improved significantly. “We’re at the point where the technologies are very robust, fast and affordable.”

This is not only important for finding receptors. The healthy tissue stored in the atlas also serves primarily as a Reference for diseases. You can see from the comparison what has changed in the sick.

Just as the Human Genome Project provides a reference for all genes, the human cell atlas is a reference for all cells, said the project’s co-founder, Aviv Regev of the Broad Institute in Cambridge, Massachusetts.

All body cells in a human have the same genome, but they use different parts of it. “It’s not enough to identify the genes for diseases, you also have to know where they are active,” says Regev. The atlas, which is freely available to researchers, can also be used to identify cells that trigger diseases.

Another team from Teichmann examined the immune system of embryos in a “Science” paper for the cell atlas and proved that immune cells develop in many organs, not only in hematopoietic ones. “Examining the cells and tissues of the human developmental stages helps us, among other things, to understand rare diseases that often occur at birth, as well as the origin of childhood tumors, which often develop during pregnancy,” explains Teichmann.

Headwork still to come

Before the current work, around 100 individual studies that analyzed the tissues of many people had already contributed to the cell atlas. A team led by Roland Eils from the Berlin Charité had already drawn up a map of the pancreas in 2020: genetically examined all the cells in it, determined their exact location and elucidated the connections between the individual cells.

“We wanted to create a resource for all researchers interested in the pancreas,” explained Eils at the time. Norbert Hübner from the Max Delbrück Center for Molecular Medicine in Berlin was in charge of an initial sketch for the heart.

The researchers analyze mRNA for the cell atlas. These are working copies of the genome that are required as instructions for the production of proteins in the cell. In the meantime, however, it is also possible to examine frozen tissue using cell nuclei alone.

The cell atlas is not yet complete. “Actually, we wanted to have a first draft ready within five years,” said Teichmann. But the pandemic got in the way. One end is open.

“We don’t even know how many cell types humans have,” admits Teichmann, in any case there are more than previously thought. “The body has over 50 tissues. Taken together, we now have a rough draft of a map with 30 tissues and 50 million individual cells,” said Teichmann. That is a very good start. However, the brain is still missing. Only small parts have been mapped, and there are around 100 brain regions in humans.

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