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The international Human Cell Atlas consortium reveals the broadest transcriptome through four simultaneous publications in the journal 'Science'
The study of the human body can be carried out at different levels. We can look at the anatomy, as has been done throughout the centuries; in cells and tissues, as was advanced with the discovery of the microscope; or in their chromosomes and genes, as has been achieved with the sequencing of our genome. Afterwards, we can apply different approaches. While Biology and biochemistry attempt to explain processes, medicine focuses on diseases to cure them.
With the advancement of science, every time something is discovered, we can delve deeper into what we already knew or combine our methods to multiply the findings. This is what happens with the new sequencing tools. The genome that we have obtained for our species is not that of a human or a specific organ, but rather is the complete sequence of an ideal model, in general. Something important still needs to be found out. What is our genome like cell by cell?
The technique that makes this possible is single cell sequencing (scRNA-seq). single cell RNA sequencing, based on RNA technology). We are talking about the sequence of a single cell, which opens a whole range of possibilities. With it, scientists map the transcriptome (of any species and any organ) at the single-cell level, with all the differences between cells, which also includes their different stages. The information obtained from these cell atlases is colossal and is organized in a database for each cell.
Your applications skyrocket. In embryology, they serve to identify where each cell comes from. In development, to trace cell lineages after birth, those of any dividing cells and their derivatives. In evolution, to compare homologous cells from different species. In medicine and pharmacy, to identify the origin of a disease, develop even finer diagnostic methods, devise new treatments or evaluate the effectiveness of a drug.
This Thursday, the magazine Science has published an important advance in this field, by presenting, with four new publications, the largest Human Cell Atlas to date. This is not the first time that our organs have been sequenced cell by cell. This line of research is of such dimensions that the person directing the work, the International Consortium Human Cell Atlas (HCA), had already revealed the cell atlases of different organs, such as the brain, lung or kidney.
To date, they have focused on individual organs and tissues. Now, comes a series of transversal maps, the so-called maps between tissues, the atlas of more than a million individual cells from 33 organs. This is a discovery with great therapeutic implications, both for common and rare diseases, for the development of vaccines, anti-tumor immunology or regenerative medicine.
Four simultaneous publications
When it comes to great discoveries, scientific journals synchronize their publication at the same time. This is what has happened with this new cellular atlas and its four corresponding articles.
En the first study, Presents itself the Tabula Sapiens, a cell atlas that provides 400 different cell types obtained from 24 organs. To assemble the data, the RNA of 500.000 live cells from different people, analyzing those that came from a single donor and making cross-comparisons controlled by their genetic background, age, environmental exposure and epigenetic effects.
El second atlas has been made from more than 200.000 frozen cells. The samples come from 8 healthy human organs from 16 donors. In addition, machine learning techniques have been used to associate atlas cells with thousands of diseases related to a single gene, as well as conditions related to complex genetic factors. The goal is to discover what types of cells and what genes are involved in certain diseases.
The human immune system has been addressed in the third studyOffering the cellular atlas of the immune system, not only blood cells, but cells that are located in the rest of the tissues. To do this, the authors of this research team have sequenced adult and developing immune cells from 16 tissues from 12 adult donors, obtaining the gene expression of more than 300.000 cells. Additionally, they have developed an artificial intelligence tool called CellTypist with which they have identified 101 different cell types, either by their characteristics or by their condition, analyzing more than a million cells.
Lastly, the fourth article, has focused on 9 prenatal tissues. Thus, a Single-cell and spatial atlas of the immune system at all stages of gestation. This work reveals that the development of blood cells and those of the immune system not only occurs in primary hematopoietic organs but also in many peripheral tissues.
Two experts assess the advances of SCRNA-SEQ sequencing
One of the pioneers and greatest experts in the world in the technique of single-cell sequencing directs several of the projects for the construction of the human cell atlas. This is Kun Zhang, professor in the Department of Bioengineering at the University of California, San Diego (UCSD). Zhang participated in the meeting Age Open Science which was held this week in Salamanca and which this media attended.
There he compared the scientific effort in obtaining the human cell atlas with the sequencing of our genome. "Twenty years ago, when the great human genome project was developed, there were several groups that worked only on one or two chromosomes, such as chromosome 21 or 13. When they put everything together, the great human genome was obtained," he explained. to this medium.
Although, on this occasion, Zhang is not part of the macro study published this Thursday in Science, he has done so previously. "This research is coordinated by a large consortium for which my group has contributed with the atlas of several human organs: the atlas of the brain, lung and kidney."said Zhang. "The publications that come out now are going to have an important meaning," he stated. "They will be like when work was done on one of those chromosomes 20 years ago, when it was about publishing the human genome."
The one of the human species is not only the only atlas that has been built. There are many other organisms, different organs or tissues. That of non-human primates (macaques) has been recently published in the magazine Nature. 35 international institutions have participated in it. Among them is the group of CYBER of Neurodegenerative Diseases led by Pura Muñoz, the 2021 Ramón y Cajal National Research Prize winner in Biology, professor of ICREA Cellular Biology at the Pompeu Fabra University (UPF) and researcher in the tissue regeneration laboratory of the National Center for Cardiovascular Research (CNIC).
Muñoz, who has not participated in the human cell atlas, is an expert in aging processes and, thanks to the scRNA-seq technique has identified different types of senescent cells, as he explained at the Salamanca meeting. From there, she has evaluated the study in humans for this newspaper and has commented on the impact that cell atlases will have on the study of age-related diseases.
Senescent cells are part of the tissues when we age. They are also present whenever there is damage," he commented. The process of tissue damage involves the appearance of these cells, "which are sometimes beneficial, but almost always harmful," he indicated. What happens is that, when As we age, the mechanisms responsible for eliminating them begin to fail and, with the passage of time, "they play a negative role on the cells in their environment. "They are guests that cause problems when there is damage and the problem is that they increase during aging," Muñoz assured.
Regarding single cell sequencing techniques, both in primates and humans, "we are going to see an increase in the number of damaged cells, which are not good, in the tissues," Muñoz highlighted. "These publications tell us how we are when we age so we can see the causes of aging. and see what we can do to reverse it. If we don't know well how we are, we can't do anything to fight it," he added.
