Scientists find cells that survive after apoptosis is triggered — ScienceDaily
Researchers at the Weizmann Institute of Science have identified a population of cells in fruit fly larvae that activate the programmed cell death mechanism but do not die and take part in repairing damaged tissue. The work was published in Nature Communications, ScienceDaily reports.
Scientists studied compensatory proliferation — the ability of epithelial tissues to rapidly recover after substantial damage. The team led by Dr. Tzlil Brown irradiated larvae with ionizing radiation and used genetic tools to track tissue regeneration.
Cells that survived the initiation of death
The researchers named the identified population DARE cells. In these cells, an initiator caspase — an enzyme that normally triggers apoptosis — was activated, but the cells survived irradiation. Within 48 hours, they multiplied, contributed to the repair of damaged tissue and provided nearly half of its regeneration.
The team also identified NARE cells, which were resistant to death but did not activate the initiator caspase. They also aided recovery but could not ensure it on their own: after DARE cells were removed, compensatory proliferation stopped completely. According to the authors, DARE cells are activated by signals from neighboring dying cells.
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The role of caspases and resistance to repeated irradiation
In DARE cells, the apoptosis process began but stopped before the activation of executioner caspases, which destroy the cell. The researchers suggest that a molecular motor protein contributes to this: it holds the initiator caspase near the cell membrane and prevents it from activating the next stage of the death mechanism. When this protein was suppressed, DARE cells died and tissue regeneration deteriorated.
After repeated irradiation, descendants of DARE cells proved to be seven times more resistant to cell death than cells of the original tissue. The scientists note that this mechanism could potentially explain why tumors that return after radiation therapy sometimes become more resistant to treatment. At the same time, the experiments were conducted on fruit flies, so further research is needed to establish whether such a mechanism operates in human tissues.
Control of tissue growth
The authors also described negative feedback between the two populations: DARE cells stimulate the growth of neighboring NARE cells, while NARE cells send signals that limit the proliferation of DARE cells. According to the researchers, this interaction makes it possible to restore tissue without excessive overgrowth.
