DARE Cells: New Clues to Tissue Regeneration

DARE Cells are helping scientists understand how damaged tissues can recover even after many cells have entered programmed cell death. Researchers from the Weizmann Institute of Science and collaborating institutions identified DARE cells in fruit fly tissue that can activate part of the cell-death machinery but resist full apoptosis. Instead of dying, these cells multiply and help rebuild damaged tissue. The study was published in Nature Communications on December 4, 2025.

What Are DARE Cells?

DARE stands for Dronc-activating radiation-induced apoptosis-resistant epithelial cells. These cells were identified in the wing discs of Drosophila, commonly known as fruit flies.

The researchers studied what happened after the tissue was exposed to ionising radiation. Radiation caused extensive cell death, but some cells remained alive. Among these surviving cells, researchers identified DARE cells, which showed activity of Dronc, the fruit-fly equivalent of an initiator caspase involved in apoptosis.

Normally, caspase activity is strongly linked with programmed cell death. However, the study found that Dronc can have another role in DARE cells. Instead of completing the cell-death process, its activity contributes to signals that support tissue regeneration.

DARE Cells Help Damaged Tissue Recover

The researchers found that DARE cells become particularly important after radiation damage. Most radiation-induced cell death occurred during the early stages of the experiment, while significant regeneration followed.

DARE cells began appearing at around 24 hours after irradiation and then multiplied during the following 24 hours. Their descendants occupied a large part of the regenerated tissue.

The study also identified another group called NARE cells, or non-Dronc-activating radiation-induced apoptosis-resistant epithelial cells. Both DARE and NARE cells contributed to tissue recovery, but DARE cells played an important role in driving the regenerative response. Removing DARE cells reduced the ability of the damaged tissue to regenerate.

How Apoptosis Usually Works

Apoptosis is a controlled form of cell death. It allows multicellular organisms to remove damaged, infected or unnecessary cells without causing the type of uncontrolled tissue damage associated with some other forms of cell death.

Caspases are important enzymes in this process. Initiator caspases activate other caspases, which then carry out many of the molecular changes associated with apoptosis.

The DARE-cell study adds another layer to this process. It shows that activation of an initiator caspase does not always have to end with cell death. In DARE cells, Dronc activity can instead participate in a pathway connected with survival and tissue repair.

DARE Cells and Tissue Regeneration

The research provides new information about compensatory proliferation, a process in which surviving cells multiply to replace cells lost after tissue damage.

The researchers found that DARE cells can promote their own growth and also influence the growth of neighbouring NARE cells. The process involves several molecular pathways, including the p38 MAPK pathway.

The study also found that the tumour necrosis factor receptor Wengen plays an important role in DARE-cell proliferation. Other proteins, including Myo1D and Myo7A/Crinkled, help control DARE-cell survival and caspase activity.

DARE Cell Descendants Show Greater Resistance

Another important finding concerns the cells produced by DARE cells. When researchers exposed the regenerated tissue to radiation again, DARE-derived cells showed greater resistance to cell death.

The study reported that DARE descendants were about seven times less sensitive to radiation-induced apoptosis, while NARE cells showed about a threefold reduction in sensitivity. This suggests that some features of the original cells’ resistance can be passed to their descendants.

Researchers described this as a type of molecular memory of resistance. Such findings could help scientists understand how tissues respond to repeated damage.

Possible Links With Cancer Research

The findings may also be relevant to cancer research, although the experiments were performed in Drosophila and do not establish a treatment for human cancer.

Cells that survive damage and become resistant to further cell death can be important in cancer biology. The researchers noted that the mechanisms involved in DARE-cell survival may provide useful clues for understanding radiation-resistant cells.

This does not mean that DARE cells directly cause cancer or that the findings can currently be applied as a cancer treatment. More research is needed to determine whether similar mechanisms operate in human tissues.

Related Research on Cell Revival in India

The DARE-cell findings also come alongside another line of research into how cells respond when they appear to be close to death. Scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad reported Programmed Cell Revival in 2025.

The CCMB team reported that cells showing signs of imminent death could, under certain conditions, regain function and contribute to tissue repair. Their work was published in The EMBO Journal and involved models including skin wounds, corneal burns, frog tadpole regeneration, nerve repair and blood stem-cell production in fruit flies.

These two studies examine different biological processes and should not be treated as the same mechanism. The DARE-cell research focuses on apoptosis-resistant cells and compensatory proliferation in fruit-fly tissues, while the CCMB work describes programmed revival from imminent cell death.

A New View of Cell Death and Repair

The discovery of DARE Cells adds to growing evidence that the relationship between cell death and tissue repair is more complex than a simple process in which cells either live or die.

The Weizmann-led study shows that some cells can activate part of the apoptosis machinery while remaining alive and becoming important for regeneration. It also shows that their descendants can retain increased resistance to later damage.

Because the work was conducted mainly in Drosophila, scientists will need further research to determine how widely these mechanisms apply to other organisms, including humans. The findings nevertheless provide a useful model for studying how damaged tissues balance cell death, survival and regeneration.