A person starts with one cell, a fertilized egg, which becomes two cells, then four, then eight, and so on, up to over 30 billion cells. They all inherit the same instruction book, the unique DNA of this person, but a neuron in the brain is nothing like a red blood cell. The bottom line is that DNA is like a piano with about 20,000 keys: genes. The cell will be one or the other depending on the activated genes. The scientific community knows that a person is like a musical conservatory with 30 billion rooms with the same piano, but humanity has so far ignored which melody plays on each keyboard. An international consortium is presenting this Thursday the most comprehensive draft of the so-called Atlas of Human Cells. This is a historic day for science.
The participating researchers, more than 2,000 in 83 countries, have already quantified some 60 million cells, one by one,” explains Aviv Regev, a forward-thinking Israeli biologist who started the project in 2016. “Our mission is to get reference cards. all human cells. Fortunately, this does not mean profiling 30 to 37 trillion adult human cells! Human cells occur in repetitive types, so we have many very similar copies,” says Regev, a researcher at the Massachusetts Institute of Technology (USA), who is on vacation.
At school, kids learn a few examples of cells — neurons, red blood cells, white blood cells, platelets… — but Regev emphasizes that “no one knows” how many types there really are. “That is why it is so important to create an atlas of human cells. We didn’t know how many genes we had until the Human Genome Project. This is a similar case,” he muses.
The Human Cell Atlas aims to catalog all cell types and their many subtypes, as well as pinpoint their location in the human body, in order to know the exact architecture of each organ: what we are made of and why disease occurs. Spanish immunologist Cecilia Domínguez Conde, born in Trigueros (Huelva) 35 years ago, is one of the main authors of the latest results of the atlas, published this Thursday in the journal Science. The researchers describe a detailed profile of more than a million cells. The novelty is that they do not focus on a specific tissue, but instead present cross-sectional data from 33 organs of the human body, such as the heart, skin, and lungs.
Two T cells (red) attack a cancer cell (white).US National Institutes of Health
Dominguez Conde’s team at the Wellcome Sanger Institute (Cambridge, UK) has focused on the cells of the immune system. Using the example of the conservatory, scientists already knew that classical music plays on the piano of white blood cells, but now they see that there are subtypes that play Mozart and that some, in particular, interpret The Marriage of Figaro in the liver and change the magic flute when passing through lungs. “We have discovered how cells adapt to different environments,” sums up the immunologist, who will head her own lab at the Human Technopole, a new research center in Milan, Italy, from June.
“The variety of cell types in the immune system is incredible. Until now, the work has focused on peripheral blood, but now we are studying cells in different tissues and seeing new mechanisms,” explains Domínguez Conde. The immunologist recalls that there is a new generation of cancer treatments, the so-called CAR-T, in which white blood cells such as T-lymphocytes are extracted from the patient’s body in order to change them in the laboratory using genetic engineering and increase their ability to destroy cancer cells. “We see that there are groups of cells playing the same tune, some playing a slightly different tune, and others playing a completely different genre. This information is very important to know which type of T-lymphocyte is best suited for the treatment of cancer or autoimmune diseases,” emphasizes Domínguez Conde.
Biology textbooks traditionally talk about 300 cell types in the human body, but the authors of the atlas found 500 types in the last million cells analyzed. Understanding this astonishing diversity will enable better vaccines, more effective cancer therapies, easier regenerative medicine, and the development of new treatments for rare and common diseases, says biologist Aviv Regev, who now holds a senior position at US biotech company Genentech.
Israeli biologist Aviv Regev, co-director of the Atlas of Human Cells.Massachusetts Institute of Technology
A mutation in a gene can cause disease, but although all cells have the same DNA, the problem only occurs in cells that have that particular gene activated. One of the consortium’s four studies published this Thursday found surprises. “We found many unexpected cells with active genes associated with the disease. For example, we observed not muscle cells, but those in muscle tissue expressing genes that cause rare muscle diseases. This is important because if we want to develop treatments, we need to know the cells in order to act on them,” notes Regev.
The Israeli biologist also highlights possible applications in regenerative medicine, a field that attempts to repair damaged organs with new cells. “In order to do this correctly, we need to create cells with the correct properties. The atlas is a reference to make sure cells created in the lab have the desired characteristics,” says the researcher, who leads an international consortium with German biologist Sarah Teichmann of the Wellcome Sanger Institute. According to Regev, the project is “halfway” to its goal.
Neuroscientist Rafael Yuste, professor at Columbia University (USA), welcomes the atlas project. “This series of results is historic. This is one of the first salvos of what will be a spate of studies in the next decade that will classify all cell types in the body,” says Yuste, who was not involved in these studies. The Spanish neuroscientist was the father of BRAIN, a billion-dollar project sponsored in 2013 by then US President Barack Obama to map the human brain.
Yuste is optimistic. New technologies called transcriptomics allow cells to be placed in narrow channels and captured one by one in oil droplets in order to analyze their active genes in a fast, automated and cheap way. “The first steps of this strategy have been impressive. For example, in the United States, the Allen Institute for Brain Sciences classified all the cells in a portion of the mouse cerebral cortex, for the first time compiling a list of all types of neurons in an area of the brain. brain,” illustrates Yuste, who participated in this project.
The professor recalls the father of neurology, Santiago Ramón y Cajal, who himself discovered in 1888 in Barcelona using a primitive microscope that neurons are individual cells. Yuste emphasizes that giant consortiums such as his BRAIN initiative and Atlas Human Cell are now engaged in this task. “It’s a huge job, but I see it as doable. And this will have a fundamental impact on science and medicine, because, in the end, everything that the brain does, or the body does, is boiled between cell types.
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