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Each human is a finely tuned orchestra of more than 37 trillion cells. Mapping this little-known world is one of biology’s greatest challenges — and one in which scientists say they just made a significant dent.
More than 3,600 researchers from over 100 countries have analyzed more than 100 million cells from over 10,000 people, according to the latest update from an ambitious project launched in 2016 to produce an atlas of every single kind of cell in the human body.
New research based on the findings, published in several papers Wednesday in Nature and its sister journals, represents a “leap in understanding of the human body,” according to the Human Cell Atlas consortium. The endeavor is similar in scale and scope to the Human Genome Project, which took two decades to complete.
“Cells are the basic unit of life, and when things go wrong, they go wrong with our cells first and foremost,” said Aviv Regev, founding cochair of the Human Cell Atlas and executive vice president for research and early development at Genentech, a biotechnology company based in South San Francisco, California.
“The challenge we’ve had is that we didn’t know the cells well enough to understand how variants and mutations in our genes are really affecting disease. Once we have this map, we’re able to better find the causes of disease,” she said at a news briefing Tuesday.
Update to a ’15th century map’
Regev compared scientific knowledge of cell biology before the Human Cell Atlas initiative with a “15th century map.”
“Now, years later, the resolution of the map is a lot higher,” she said. “It’s more like Google Maps, where you have a very high-resolution view of the real topography, and then on top of that, you have the street view that really explains to you what is going on there. And on top of that, you can even see the driving patterns, like the dynamic changes that happen during the day,” she added.
“That is the leap that we have done … but we still have work to do.”
A challenge is that different types of cells can look morphologically indistinguishable under a microscope but can vary dramatically at the molecular level. What’s more, cells change as humans age and in relation to the external environment.
Advances in single-cell sequencing technology allow scientists to understand how genes in an individual cell are switched on and off by analyzing RNA, which reads the DNA contained in each cell. This technology, combined with powerful computing and artificial intelligence methods, allows researchers to create an ID card for each cell type.
It was once thought there were only 200 or so different types of cells. Scientists now know there are thousands.
The consortium is building maps of 18 biological networks, the most complex of which is the brain, and the first complete draft of the Human Cell Atlas will be published in 2026, Regev said. The cell atlas aims to fill in a missing link between genes, diseases and treatment therapies.
“This is just an incredibly exciting journey, in terms of our voyage through the human body and discovery of fundamental new insights into our cells,” said Sarah Teichmann, founding cochair of the Human Cell Atlas and a professor at the Cambridge Stem Cell Institute at the UK’s University of Cambridge.
Milestones could unlock new treatments
The milestones made public Wednesday include mapping all the cells of the gut; producing a blueprint of how human skeletons form in utero; understanding the basic structure of the thymus, an organ that plays a key role in how the immune system functions; mapping the molecular architecture of the placenta; and building an atlas of human vascular cells.
The gastrointestinal tract atlas, which includes the tissues of the mouth through to the esophagus, stomach, intestines and colon, was created with data from 1.6 million cells and revealed a cell type that might play a role in chronic conditions such as inflammatory bowel disease.
The early skeleton map found certain genes activated in early bone cells that might be linked to an increased risk of developing hip arthritis as an adult. “Having a clearer picture of what is happening as our skeleton forms, and how this impacts conditions such as osteoarthritis, could help unlock new treatments in the future,” said Ken To, a researcher at the Wellcome Sanger Institute in England who coauthored that research, in a statement.
English scientist Robert Hooke discovered cells in 1665, looking at cork under a microscope. He introduced the word cell because the patterns made by the cellulose walls of dead cork reminded him of blocks of cells used by monks. However, it was 200 years later when scientists finally understood that cells were the fundamental unit of the human body.
Unlike the original draft human genome, which was predominantly based on a single individual, the cell atlas aims to be globally representative and involves researchers and human tissue samples from around the world.
The project has already led to some significant breakthroughs, including the discovery of a previously unknown cell type in the respiratory tract called an ionocyte. Study of this rare cell type could lead to new ways to treat cystic fibrosis, a genetic condition caused by a gene that affects the movement of salt and water in and out of cells.
During the Covid-19 pandemic, the Human Cell Atlas community used the available data to reveal that the nose, eyes and mouth were most vulnerable to infection.
“It was only clear through the Human Cell Atlas data that those cells were … entry points before the virus continued into the internal organs. That really illustrates quite simply how important a healthy reference map of the human body is, and a deep molecular understanding of ourselves,” Teichmann said.
Jeremy Farrar, chief scientist at World Health Organization, who was not involved in the research, agreed that insights emerging from the atlas are “already reshaping our understanding of health and disease.”
“This landmark collection of papers from the international Human Cell Atlas community underscores the tremendous progress toward mapping every single kind of human cell and how they change as we grow up and age,” Farrar said in a statement.