More than 3,600 scientists are building a manual of all human cells: ‘A Google Maps of biology’

In science fiction films, we often see characters entering machines that scan their cells to detect illnesses and cure them. While the concept of a robot doctor may belong to dystopian visions, science is working toward a technology that could help real-life medical professionals diagnose diseases early and accurately, and prescribe personalized and precise treatments. Though this goal remains distant, it is one step closer today. A series of over 40 studies published on Wednesday brings us closer to building a 3D atlas of all human cells — a detailed and complete digital manual of the body.

As with any major scientific endeavor, the announcement of the Human Cell Atlas (HCA) in 2016 wasn’t the headline of the day. It began as an ambitious but relatively modest project, introduced in London by a group of about a hundred scientists led by two biologists, Aviv Regev — now at Genentech — and Sarah Teichmann — now at the Cambridge Stem Cell Institute. Over the years, the HCA has expanded to include over 3,600 members from around the world, supported by more than a hundred institutions. Today, it is one of the largest global consortia in the field of Big Science, surpassing even the size of the Human Genome Project at its peak.

The HCA is divided into 18 networks, each focused on a specific organ, tissue, or system. Researchers have already analyzed over 100 million cells from approximately 10,000 individuals, ensuring a broad representation of human diversity. Applying precision genomic techniques to each individual cell, together with powerful bioinformatics and artificial intelligence (AI) tools, they are mapping which of the 20,000 genes in the human genome are active in different cell types. The idea is to create a kind of “cellular ID” for each profile, identifying the proteins they produce, how they function, and how cells communicate within tissues, all captured in intricate, navigable spatial maps. As Teichmann explains, the HCA will be “a kind of Google Maps of cellular biology.”

The HCA has contributed more than 440 studies, and its data portal already offers atlases of the nervous system, the lungs and the eye. These atlases will be superimposed to form a “complete reference map of the healthy human body,” says Teichmann. The atlas not only covers the adult organism, but also the development of organs and tissues from the embryonic and paediatric stages, which are often the cause of ailments.

Causes of the disease and new drugs

The more than 40 studies published on Wednesday in various journals of the Nature group mark “a crucial moment for the HCA community,” according to Regev. This major collaborative effort spans multiple areas, including the development of the placenta, skeleton, and nervous system, as well as the impact of genetic variations on cell diseases. The studies also explore the effects of Covid-19 on the lungs and the function and alterations of the digestive system, among other topics.

These findings will be incorporated into the first draft of the Human Cell Atlas, which is set to be published in 2025-26. The atlas will be made available online with open access and will continue to grow, ultimately encompassing billions of cells from every organ and tissue in the human body, which is made up of around 37 trillion cells.

According to Regev, “the main future — and current — benefit is the progress in discovering the causes of diseases and the development of medicines.” Scientists are already using the atlas daily for these purposes. As the HCA co-founder explains, researchers compare cells from diseased tissues — such as biopsies from tumors or patients with autoimmune conditions — with healthy reference cells. The differences in their composition and gene expression offer valuable insights into the origins of the disease and potential treatments. “At Genentech, we have a clinical trial for inflammatory bowel disease that we have undertaken in part thanks to the large-scale data analysis from the atlas,” says Regev.

The study cited by Regev is part of one of the studies published on Wednesday, which identifies a specific type of cell involved in inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. Co-led by Teichmann and published in Nature, this study is the result of a collaboration between scientists from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) — based at the Hospital Clínic de Barcelona — and Spain’s Center for Biomedical Research Network on Liver and Digestive Diseases (CIBEREHD).

The researchers compiled existing RNA sequences — the product of genes that are used to create proteins — from single cells, as well as new samples, bringing the total to 1.1 million healthy cells of 137 different types from across the entire digestive tract, both in adults and during development. The digestive atlas also includes an additional half million cells affected by diseases such as stomach and colorectal cancer, celiac disease, ulcerative colitis, and Crohn’s disease.

Misguided cells in intestinal inflammation

By comparing the transcriptional profiles — the RNA present in the cells — the scientists identified certain cells in the large intestine of patients that resembled cells found in the stomach or small intestine. “The presence of cells corresponding to another tissue is common in the context of chronic inflammation,” explains Azucena Salas, the director of the Spanish group. While this phenomenon had previously been attributed to the healing of wounds in the intestinal wall, the study revealed a new insight: these misdirected cells, generated from stem cells during tissue repair, actually contribute to the inflammation itself. “They are not mere spectators, but actively participate in the intestinal damage,” says Salas.

Rasa Elmentaite, co-director of the study at Ensocell Therapeutics, suggests that processing the findings from the digestive atlas using AI platforms will facilitate the design of a new generation of therapies. “Despite the critical role of epithelial cells in the progression of inflammatory bowel disease, available treatments do not effectively target them,” she says.

Organoids — miniature, lab-grown versions of organs and tissues — are already being used in research to better understand organ functions, diseases, and to test potential new drugs. These organoids will play a central role in the development of new therapies.

“To ensure that an organoid correctly represents the organ, we need to compare its cells to a reference atlas of the organ, which is what the HCA provides us,” explains Regev. Looking ahead, regenerative medicine’s long-awaited promise is also on the horizon: “Understanding normal cell development will help biomedical engineering create cells that can be introduced into the body as therapy.”

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