In science fiction movies we have seen how someone is put into a machine that scans their cells to detect their disease and cure it. He is a dystopia, but science does aspire to a technology that could help real professionals diagnose any ailment early and accurately, and dictate. Although that is a very distant goal, today it is closer: a battery of more than 40 studies published this Wednesday moves towards the construction of a 3D atlas of all human cells, a detailed and complete digital instruction manual for the organism.
As with any great scientific project, (HCA) was not the most talked about news of the day. At that time it started as an ambitious initiative, but of still modest dimensions, launched in a presentation in London by a hundred scientists led by two biologists, Aviv Regev – today at the Genentech company – and Sarah Teichmann – today at the Cambridge Stem Cell Institute. —. Over the years, the HCA has grown to more than 3,600 members from a hundred countries, with funding from more than a hundred institutions around the world. Today it is one of the large global consortiums of what is known as Big Scienceand it is older than the .
The HCA is organized into 18 networks, each dedicated to an organ, tissue or system. Scientists have already characterized more than 100 million cells from about 10,000 individuals, taking special care to ensure that all the broad human diversity is represented. Applying , together with powerful bioinformatics and artificial intelligence (AI) tools, they investigate which of the 20,000 genes of the human genome are active in each type of cell, which configures something like the DNI of each cellular profile; what proteins they produce and how they act, the communication between cells and their architecture in tissues, all in detailed navigable spatial maps. In Teichmann’s words, it will be “a kind of Google Maps of cell biology.”
So far the HCA has provided more than 440 studies, and the data portal already offers atlases of the nervous system, the lung and the eye, which will be superimposed on others to form a “complete reference map of the healthy human body,” he summarizes. Teichmann. The atlas not only covers the adult organism, but also the development of organs and tissues from the embryonic and pediatric stages, which are often the origin of ailments throughout life.
Causes of the disease and new drugs
The more than 40 studies published today in various magazines of the group Nature They represent “a crucial moment for the HCA community,” says Regev; a great joint push to the project that covers multiple fronts, from the development of the placenta, the skeleton and the nervous system, to the impact of genetic variations on cell diseases, through the effects of COVID-19 on the lungs or the function and alterations of the digestive system, among other fields.
All of these results will be integrated into the first draft of the HCA, which will be published in 2025-26, available online with open access, and will continue to grow to include a volume of billions of cells in each and every organ and tissues of the human body, composed of.
According to Regev, “the main future – and current benefit – is the advance in the discovery of the causes of the disease and the development of medications. “Scientists already use the atlas every day for these purposes.” Thus, explains the co-founder of the HCA, researchers compare cells from diseased tissues, such as biopsies of tumors or patients with autoimmunity, with healthy reference cells, and the differences in their composition and expressed genes are clues to the origin. of the disease and its possible treatments. “At Genentech we have a clinical trial on inflammatory bowel disease that we have undertaken in part thanks to the analysis of large-scale data from the atlas,” highlights the scientist.
The essay that Regev cites is related to one of the studies published today, which identifies a type of cell involved in inflammatory bowel diseases such as ulcerative colitis or Crohn’s disease. The study, co-directed by Teichmann and , is a collaboration that includes a group of scientists from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) —based at the Hospital Clínic of Barcelona— and the Red Biomedical Research Center of Liver and Digestive Diseases (CIBEREHD).
Researchers have collected existing sequences of RNA – the product of genes that are used to create proteins – from individual cells, along with new samples, bringing together a total of 1.1 million healthy cells of 137 different types over a period of time. the entire digestive tract, both adult and developing. The digestive atlas is completed with another half a million cells sick with ailments such as celiac disease, ulcerative colitis and Crohn’s disease.
Wrong cells in intestinal inflammation
By comparing transcriptional profiles – the RNAs present in cells – scientists have observed in the large intestine of patients certain cells similar to those in the stomach or small intestine. “The presence of cells that correspond to another tissue is common in the context of chronic inflammation,” says the director of the Spanish group, Azucena Salas. The scientist explains that this had been assigned to the healing of wounds in the intestinal wall, but there is a new finding: these erroneous cells, which are generated during repair, promote inflammation itself. “They are not pure spectators, but rather actively participate in intestinal damage,” says Salas.
According to study co-director Rasa Elmentaite, from the company Ensocell Therapeutics, processing the findings from the digestive atlas in AI platforms will help design a new generation of therapies. “Despite the critical role of epithelial cells in the progression of inflammatory bowel disease, available treatments do not act effectively on them.”
In these new therapies, organoids will play a central role, miniature versions of organs and tissues that are already used in laboratories to deepen our knowledge of their functions and diseases, and to test new drugs. “To know that the organoid correctly represents the organ, we need to compare its cells with a reference atlas of the organ, and the HCA gives us that,” says Regev. On the horizon is the long-awaited promise of regenerative medicine: “Understanding normal cellular development helps biomedical engineering create cells that can be introduced into the body as therapy.”
