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“Murderer” Cells Murder Innocent Cells

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Scientists have found that a quarter of testicular progenitor cells are “killed” by phagocytes, despite the fact that these cells are not doing anything “wrong”.

Research from the University of Haifa has identified killer cells.

A process that involves the “killing” of newly generated living cells was first discovered in recent research conducted at the University of Haifa. The research, which was described in the prestigious journal Scientists progressfound that throughout the process of cell differentiation in fruit flies, phagocytic cells consume and destroy healthy living cells.

“We discovered that phagocytes can function as ‘murderers’. It is well known that phagocytic cells swallow and dissolve dead cells, but we show for the first time that they also kill newly created normal cells. Essentially, we have characterized a novel cell death mechanism. The more we know about the mechanisms of cell death, the better we understand how to deal with various diseases, including cancer,” explained Professor Hilla Toledano, Head of the Department of Human Biology at the University of Haifa and author of the study. .

The origin of several bodily tissues, including skin, hair, stomach, and testicles, can be traced back to stem cells. By continually supplying new cells to replace old ones, these powerful stem cells enable tissue replenishment. Each stem cell in this process divides into two cells, one of which is saved for future use and the other grows to take the place of the lost cell in the tissue.

In the current investigation, Prof. Toledano, Prof. Estee Kurant and a group of scientists from the University of Haifa examined the sex cells of fruit flies. Since many molecular processes in fruit flies and humans are similar, they can be used as an effective model in this situation.

Fruit fly studies are useful because of the ability to monitor processes in living tissues and the simplicity of genetic alteration, which allows exact identification of cellular processes. Six Nobel Prizes have been awarded over the years to scientists who have discovered biological mechanisms in fruit flies that are conserved in humans.

As mentioned earlier, the division of a stem cell into two cells – a stem cell and a cell called a progenitor – triggers the process of sperm differentiation in male fruit flies. This process continues until the formation of functional sperm. Researchers already knew that a quarter of these progenitor cells perish and do not develop into sperm from previous studies. The goal of the current study was to better understand what happens to these cells.

The body has a well-established and crucial mechanism called cell death. Under normal circumstances, cells have the ability to “commit suicide” when a serious mutation has occurred or after they have achieved their goal. The phagocytes come to “eat” the dying cells, effectively carrying away their contents and dissolving them. We know that phagocytes sometimes “eat” immune system cells that have finished their work of defending the body against intruders.

In the current study, the researchers found that the phagocytes “kill” a quarter of the testicular progenitor cells, although these cells are not doing anything “wrong” and are simply differentiating; they are still new cells and they are not abnormal in any way.

In the first stage, the researchers inhibited the feeding abilities of the phagocytes and found no dead cells in the tissues. In other words, phagocytes are responsible for the death of progenitor cells.

In the second step, the researchers used real-time imaging to monitor living tissue and found that progenitor cells are swallowed alive by the phagocyte, and only then the death process is initiated. “We have discovered for the first time a process leading to the ‘killing’ of completely normal cells. We still don’t know why this is happening. Perhaps this process aims to provide nutrients to maintain a functional population of stem cells throughout the life of the organism,” Professor Toledano suggested.

In addition to understanding a new mechanism, this study may contribute to our ability to develop drugs and means to control cell death, and particularly, of course, to treat cancer. “Tumors are characterized by constant growth and disruption of the natural cell death process. If we manage to introduce into this process phagocytes capable of eliminating living cancer cells, we will be able to control the growth of the tumour. The more we learn about the mechanisms of cell death, the better we can harness these processes to get rid of cancer cells,” Professor Toledano concluded.

Reference: “Phagocytic cyst cells in Drosophila testes eliminate germ cell progenitors via phagoptosis” by Maayan Zohar-Fux, Aya Ben-Hamo-Arad, Tal Arad, Marina Volin, Boris Shklyar, Ketty Hakim-Mishnaevski, Lilach Porat-Kuperstein, Estee Kurant and Hila Toledano, June 17, 2022, Scientific advances.
DOI: 10.1126/sciadv.abm4937