In a massive collaborative effort, researchers have compiled the most comprehensive atlas of healthy human cells to date, mapping the positions of more than one million cells in 33 different organs.
This incredible feat provides a comprehensive reference to help us better understand human health, disease, treatments and vaccines, with the goal of mapping every type of cell in the human body as part of the International Atlas of Human Cells.
“You can think of it as a Google Maps of the human body,” Sarah Teichmann, a cell geneticist at the Wellcome Sanger Institute, told a news conference.
“It’s really this view of the street maps of individual cells and their location in tissues that we’re aiming for.”
Four studies, involving more than 2,300 researchers in 83 countries, have harnessed improved laboratory technologies and advances in machine learning to map, compare and dig deeper into the building block of life: the cell.
New algorithms were key to helping them uncover important molecular patterns among the disordered biological noise.
“People often think that the genome is the blueprint for the organism, but that’s not really correct. The genome is more of a list of parts, because each type of cell uses a different set of parts,” Steve explained. Stanford bioengineer Quake at the press conference. .
“What we have been able to do collectively here is help understand and interpret how different parts of the genome are used to define different cell types and create molecular definitions for all the different cell types that we have studied collectively in these articles.
The huge datasets, compiled through the generosity of tissue donors, will allow us to make connections between these cells for a more complete and holistic perspective of our biological processes and the disturbances that lead to disease.
For example, “we may have genetic variants in our DNA that are shared by all cells in the body, and yet the disease itself will only manifest in certain tissues, in certain organs, and it will happen depending on the genes cells actually use,” notes MIT computational biologist Aviv Regev.
His study, led by MIT computational biologist Gökcen Eraslan, developed experimental processes to accurately profile more cell types than ever before, to help compile and also search the atlas.
“In our study, we have shown that this approach can generate crucial insights into the role of cells and tissues in many diseases, which will trigger new scientific and biomedical investigations with a common goal of revolutionizing medicine,” said Regev.
The Healthy Cell Atlas has already revealed new cell types, cell communication patterns, tissue-specific cellular characteristics, microbiome patterns, cell states important to disease, and much more.
The researchers supplemented their findings with experiments, such as testing signaling molecules in organoids to confirm their findings.
One of the datasets, called Tabula Sapiens, contains the molecular profiles of 400 different cell types (each type imaged and annotated by experts), obtained from single-cell RNA sequencing of nearly half a million of living cells.
He discovered how some cell types look the same no matter where they are in the body, while other cell types look wildly different from each other in different tissues.
Although researchers have already discovered many genes that lie behind diseases, we still don’t know much about the tissues and environments in which these genes manifest. Cell mapping datasets allow researchers to identify these tissues and study which cell types participate together to form a disease, providing more targets for treatments.
Additionally, a healthy cell atlas can also reveal where a molecule targeted for treatment will be expressed in the body, allowing us to see if there will be toxicity, Regev explained.
“We also took the opportunity to look, in the case of the gut, at the non-human cells that are there, the microbiome, based on location,” Quake said.
“There’s a really rich and complex structure to the species as you move through the intestines.”
Our symbiotic microbes play a huge role in our health.
The new findings were described in a collection of articles; a few teams have zoomed in specifically on the immune system, looking for the locations of immune cells and their developmental maturation.
Genomics Chenqu Suo and his team have discovered a new type of immune cell that appears to be involved in the recognition of self antigens. Teichmann suspects that its role is to direct the immune system to be tolerant of our own healthy tissues.
These are just a few examples of the exciting possible applications of a healthy cell atlas, and there will be even more to discover as new and experienced scientists continue to learn from them.
“The Human Cell Atlas is very committed to including variation in humans and not just a narrow view of them,” Regev said. “But these are still the early days.”
“Variation will be the next generation of the Human Cell Atlas,” Teichmann added.
These studies have all been published in Science here, here, here and here.