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New technology allows a "peek" into what is happening inside cells

The technology, developed by Weizmann Institute of Science scientists, may be a powerful tool in the development of new treatments for cancer and many other diseases

Imaging of communication between two cells of the immune system - a "combatant" T cell and a "suppressor" myeloid cell. The yellow sparks are meant to illustrate intracellular processes that can be detected using the new method

A glimpse into the inner world of cells, a close examination of their activity and close monitoring of their internal communication: a new technology developed by Weizmann Institute of Science scientists allows researchers to see in greater detail than ever before what is happening inside tens of thousands of individual cells - at once. As published today in the scientific journal Cell, through the use of this technology, the scientists discovered a new subset of cells that belong to the innate immune system, and "collaborate" with cancerous tumors by suppressing the body's immune activity against cancer. Neutralizing these cells in mice led to a significant improvement of the immune system's response against the tumors and the eradication of the cancer.

The research group led by Prof. Ido Amit from the Department of Immunology has already made significant progress in the past in the ability to look closely and characterize cells with high resolution, when it developed a method for sequencing the RNA genetic material from each cell separately (single-cell RNA-seq). The new technology, known as INs-seq (intracellular staining and sequencing), makes it possible to measure the activity of intracellular proteins at the same time as the RNA content, thus characterizing biochemical processes and pathways that distinguish each and every cell in the various tissues of the body. To achieve these results, researchers Yonatan Katzenlenbogen, Fadi Shiban, Adam Yelin and Dr. Assaf Wiener developed new methods to penetrate the cell envelope without damaging its genetic content. The great wealth of "internal information" discovered in them greatly improves the ability to distinguish subtle differences in the function and activity of different subtypes of cells - this is in contrast to the existing methods that allow cells to be characterized only by measuring their envelope proteins, which limits the ability to separate cells with activities Different and sometimes even opposite.

Prof. Amit compares the existing methods for characterizing cells to choosing watermelons: from the outside, all watermelons are similar, but when you open them, significant differences in taste and texture are revealed. Similarly, the new method makes it possible to distinguish between different subtypes of cells that look completely identical from the outside. Thus, although the main groups of the cells of the immune system were identified many decades ago, there are many dozens of subgroups that have not yet been identified, and their activity may be significant. "Certain subtypes of immune cells, for example, may help cancer escape the immune system, cause tissue destruction due to an overreaction to the virus, or attack the body's own tissues, as happens in autoimmune diseases. Until now, we didn't have a method sensitive enough to distinguish between these subtypes and the others," explains Shivan.

Using the technology they developed, the scientists tried to examine why the immune system fails to identify cancer cells and eliminate them - and whether cancerous tumors may "hijack" and "manipulate" certain cells of the immune system, so that they are protected against the rest of the system's cells. "Immune reactions are supposed to be, usually, short-term, so the immune system has mechanisms to stop them, for example by means of suppressive immune cells", explains Yelin. "A cancer tumor can take advantage of these mechanisms to recruit suppressive cells to the tumor environment - thus preventing other cells of the immune system from recognizing and eliminating the cancer cells."

The researchers were able to identify special cells of the innate immune system, belonging to the myeloid cell group, which suppress the activity of "gut" immune cells called T cells. This subtype of suppressive myeloid cells was unknown to the scientific community until now. It was identified using the new technology and characterized by the presence of a receptor called TREM2 on the cell envelope. For the most part, cells carrying this receptor are essential for preventing excess tissue damage following an injury or calming an inflammatory response, but Prof. Amit and his team previously identified another role of this receptor on the cells of the immune system involved in Alzheimer's, metabolic syndromes, and other immune-related pathologies.

Following the findings, the researchers are now developing an immunotherapy treatment based on antibodies specific to this receptor. "Since the receptor is expressed only in disease states", says Dr. Wiener, "damage to it is not expected to damage the healthy body cells". Initial findings for the feasibility of treatments based on the TREM2 receptor were presented by the scientists in a cancer model in mice. The scientists showed that in mice in which these receptors were silenced, the ability of T cells to attack the cancer improved - and the tumors shrank significantly.

The "Yade" company, an arm of the institute's intellectual property commercialization, is currently working with Prof. Amit's laboratory to develop an antibody to 2TREM for clinical use. In addition, great interest was registered in the new INs-seq technology. "Besides cancer, identifying new subtypes of immune system cells will allow a deeper understanding of the mechanisms that cause autoimmune diseases, neurodegenerative diseases and many other diseases. The INs-seq technology may help researchers to identify these subtypes and lead to the development of new treatments," says Katznelnebogen.

Also participating in the study were Dr. Ido Yaffe, Dr. Demetri Savticini, Dr. Diego Hayitin, Dr. Hamotel Borenstein Ovitz, Dr. Adi Moshe, Dr. Hadas Keren-Shaul, Dr. Mirav Cohen, Dr. Shuiyang-yin Wang, Dr. Baugo Lee, Eyal David and Dr. Tomer Meir Selma.

More of the topic in Hayadan:

3 תגובות

  1. It seems to me that the watermelon house is a picturesque but accurate description. Until now there was an option to sequence the RNA of cells or to mark proteins. Because to mark a protein you have to pierce the cell and then the RNA escapes/is destroyed.

  2. Nice and all the best..but why wasn't it detailed what the new technology is?? And as if the entire article and title is based on it..

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