The goal of the more than 2,000 members of the international Human Cell Atlas consortium is to map all cell types in the human body and now they are closer thanks to “a great feat”: the publication of detailed maps of more than a million individual cells in 33 organs.
These are the most comprehensive cross-sectional cell atlases to date, the data of which, published in four articles in the journal Science, will have many therapeutic implications, including better understanding of common and rare diseases, vaccine development, antitumor immunology and regenerative medicine.
Until now, the consortium has focused primarily on gaining deep cellular insight into individual organs, tissues, or small subsets of tissues, but this new work, which also uses machine learning through artificial intelligence, goes further.
Researchers, among others, from the Wellcome Sanger Institute (United Kingdom), the Broad Institute of MIT and Harvard, and the Chan Zuckerberg Biohub -the latter in the United States- are behind these freely accessible maps, which allow specific cell types to be compared with great detail.
Two of these studies are focused on the immune system. Historically, knowledge of this has been limited primarily to the function of cells circulating in the blood, but immune cells in tissues play a critical role in maintaining health and fighting infection.
In one of them, researchers from Wellcome Sanger and the University of Cambridge sequenced the RNA of 330,000 individual immune cells from throughout the body to understand their function in different tissues. This is key because the RNA is the one that carries the DNA instructions for the functioning of the cell and only at the individual level can it be understood how a cell works.
The team developed a machine learning tool (CellTypist) to mechanize the identification of the cell type from its collection. With this tool, they observed about a hundred different types of immune cells, such as specific macrophages, T cells and B cells, and their distribution in different tissues.
This could have “great implications” in infection control, explains Sarah Teichmann, lead author of the work, for whom it could also serve as a framework for the design of vaccines or to improve the development of immunological therapies against cancer.
The other study, also from the same institutions, describes a comprehensive atlas of the developing immune system across organs, revealing the tissues involved in the formation of blood and immune cells. It also shows the types of cells that are lost as we grow, says a statement from the Trust.
In addition to identifying types of immune cells, research shows that certain types follow specific distribution patterns in tissues; Understanding this may help how treatments targeting these cells might affect other tissues, according to Joanne Jones of Cambridge.
The Tabula Sapiens consortium is behind the third study. With the rise of single-cell biology, unique tools, techniques, and on-chain procedures have been created that pinpoint precisely which genes are expressed by the individual cells that make up tissues and organs.
This promises to open avenues for new therapies, since diseases usually affect specific cell types, sums up Chan Zuckerberg.
Here, the researchers present a comprehensive atlas mapping the gene expression of nearly 500,000 living cells from tissues and organs, including lungs, skin, heart, and blood. It is the first to include histological images of the tissues, among other novelties.
The fourth of the texts talks about frozen tissues and sheds light on rare and common disease genes.
One of the challenges of single-cell atlases is to help map specific cell types in which pathological genes act – causing rare diseases such as muscular dystrophy or contributing to the risk of common diseases such as heart disease.
To do this, it is necessary to outline the variety of cells, sometimes hidden and unknown, including those of skeletal muscle, fat and neurons, difficult to capture; also, counting cells from a large number of individuals, which requires collecting and freezing tissues.
The Broad Institute presents for the first time a map of individual cells contained in frozen samples from eight organs and compiles a cross-tissue atlas with more than 200,000 profiles of the RNA contained in cell nuclei.
This helped them identify the RNA contained in a single cell nucleus; this map is of such definition that it allows to find a single damaged cell within a tissue, even frozen.
In addition, using machine learning algorithms, the cells in this atlas were associated with thousands of key genes that make it possible to identify damaged cell types that could be involved in diseases.
For José Manuel Bautista, Professor of Molecular Biology at the Complutense University of Madrid, these publications -in which he does not participate- are important because they represent the beginning to start dissecting the components that regulate each cell of each tissue.
“Until now, tissues have been seen as homogeneous, formed by groups of identical cells, but from now on they will be seen as structures formed by the individual functions of each cell, and how the relationships between them maintain normalcy and cause disease”, concludes.