While they are reading these lines, some 30 billion cells are working overtime in their body with the sole objective of keeping them alive in the best possible conditions. Despite the fact that this huge mass of cells share the same genetic code, each one uses this ‘instruction manual’ in a different way. This explains why, despite the fact that they all come from the same two initial cells, an egg cell and a sperm cell, some end up differentiating into red blood cells, others into neurons, or into fibroblasts and so on.
Until now, it was unknown what part of the genome each cell ‘read’ to fulfill its functions, nor what happened so that it stopped fulfilling them or fulfilled them poorly and caused disease. In addition, not all the types of cells that made up the body’s tissues and organs were known, nor what state they were in. Or if they were the same when they were present in different parts of the body. As if, in the field of sports, we did not know what kind of players – defenders, forwards, full-backs – make up a basketball or water polo team. Or if the handball goalkeeper is the same as the soccer goalkeeper.
The findings open the door to a better understanding of rare diseases; to develop more precise and efficient vaccines, immunotherapies for cancer and regenerative medicine treatments.
Now, an international consortium signed by more than 2,300 members from 83 different countries, called the Human Cell Atlas (HCA), has published four exhaustive papers in the journal Science in which they manage to outline a highly detailed map – the most detailed to date – of more than a million cells present in 33 parts of our body.
It is a milestone that provides new and valuable knowledge about human biology and, specifically, about the immune system; and that has made it possible to identify cell types that were previously unknown. The findings outlined in the studies open the door to a better understanding of rare diseases; to develop more precise and efficient vaccines, immunotherapies for cancer and even promote regenerative medicine treatments.
“This is a Google Maps of the organism, in which we provide the Street View view of individual cells and locate them within the tissues,” compares Sarah Teichmann, a researcher at the Wellcome Sanger Institute, co-author of two of the studies and promoter of the HCA in 2016.
These four works characterize cells at the molecular level. “The main cell types were already known, of which we had cytological knowledge, by studying their shape, and we knew their function,” says Roderic Guigó, coordinator of the bioinformatics program at the Center for Genomic Regulation (CRG) in Barcelona, who He is a member of the ethics committee of the HCA.
“But within these large groups there are subgroups: not all neurons are the same and that is difficult to distinguish when studying them under the microscope. This work has allowed us to increase resolution”.
Continuing with the metaphor of sports that we used at the beginning of this article, the atlases of human cells that are now published, openly, available to the entire scientific community, allow us to know if a player is a left winger or a right back. And differentiate precisely what a water polo goalkeeper is like and what a hockey goalkeeper is like and the exact functions they fulfill in his specific environment.
Unprecedented knowledge about the immune system
The first two works, led by the Wellcome Sanger Institute in Cambridge (United Kingdom), focus on immune cells, both during embryonic development and in adult tissues and organs. Traditionally, scientists limited themselves to studying the role of defense cells circulating in the blood; In this case, the researchers analyzed the organs and tissues in which the immune cells are generated, the regions of the body to which they migrate, such as the intestines, the skin or the lungs, and also those in which they mature, such as the lymph nodes. and the spleen.
Defense cells play a crucial role in maintaining health and fighting infection. The researchers were able to compare specific types of these cells, such as T lymphocytes, present in different tissues of the body, and identified a subtype of memory T cells in a variety of regions of the body. In one of the studies, led by the Spanish researcher Cecilia Domínguez Conde, they read the genome of 330,000 defense cells from 16 body tissues with the aim of understanding what specific functions they performed. According to Teichmann, “we have found the molecular GPS system for immune cells that are located in specific organs throughout the body.”
They also used artificial intelligence, specifically a machine-learning algorithm they dubbed CellTypist, with which they automated the identification of cell types. In this way, they have managed to outline an atlas of immune cells that reveals how they interact with each region of the body, the similarities and differences that these cells share based on the tissue in which they are found and the stage of life. This knowledge opens the door to improving therapies aimed at boosting an immune response, such as vaccines or cancer treatments.
“We have found the molecular GPS system for immune cells that are located in specific organs throughout the body.”
The third study, led by the Broad Institute of MIT and Harvard University, analyzes 210,000 cells with the aim of identifying genes that cause disease. Also using machine-learning algorithms, they were able to associate the cells in the atlas with 6,000 monogenic diseases (caused by a single gene) and more complex genetic diseases, which will allow progress in the study of these diseases.
Aviv Regev, a researcher at the Broad Institute and co-author of this study, explained at a press conference that they have found that a type of cell that is not muscle is, for example, involved in muscular dystrophy. “There is a mutation in genes that are not expressed by muscle cells and that affects other cells that are in the muscles, critical for muscle function and that can cause dystrophy,” Regev points out.
Finally, in the fourth cell atlas, Tabula Sapiens, a team made up of more than 160 experts manages to map gene expression in almost half a million living cells from 24 tissues and organs. They offer the molecular definition of more than 400 cell types. Among other findings, they have seen that a protein called CD47, which is involved both in cancer and in the accumulation of plaques in the walls of the arteries, differs greatly between cells. That discovery could make it easier to design more targeted drugs with fewer side effects.