Surprise: Lost stem cells naturally replaced by non-stem cells, fly research suggests

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Johns Hopkins researchers have discovered an unexpected phenomenon in the organs that produce sperm in fruit flies: When a certain kind of stem cell is killed off experimentally, another group of non-stem cells can come out of retirement to replace them.

The discovery sheds light on the tiny "environments" that stem cells occupy in animal bodies and may help explain how stem cells in tumors replenish themselves, the researchers report in the May 8 issue of the journal Cell Reports. Damage of the kind duplicated in the laboratory occurs naturally after exposure to radiation and perhaps also after ingestion of toxic chemicals such as those used in chemotherapy.

The research group, led by Erika Matunis, Ph.D., a professor of cell biology at the Johns Hopkins University School of Medicine, has been using the fruit fly as a model living system in which to study stem cells in their natural state. Most stem cell research is done on cells grown in the laboratory, but in real life, stem cells reside in tissues, where they are sequestered in tiny spaces known as niches. Adult stem cells keep dividing throughout life to make various kinds of cells, like new blood cells and germ cells.

Matunis's group studies such niches in fruit fly testes, the sperm-producing organs shaped like a coiled tube whose end houses a niche. In the niche are three kinds of cells: germ line stem cells, which divide to produce sperm; somatic cyst stem cells, which make a kind of cell that helps the sperm-producing cells out; and hub cells, which make signals that keep the other two kinds of cells going.

The hub cells are not stem cells; they have settled on their final form, incapable of dividing further or changing their functionor so everyone thought.

However, in a bid to figure out what happens when the somatic cyst stem cells are killed off, Matunis suggested that graduate student Phylis Hti figure out how to best do away with them, thinking the task would be straightforward.

Instead, she says, "it took a lot of heroic, patient combinations" of different genes working together to kill the somatic cyst cells, Matunis says.

"When we finally figured out a way to kill all of the somatic stem cells, we thought that the rest of the tissue would probably just empty out," she says. In 35 percent of testes, that's just what happened. But in the rest, the somatic stem cells grew back.

This was a surprise, Matunis says, and left a puzzle: Where were the new somatic stem cells coming from?

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Surprise: Lost stem cells naturally replaced by non-stem cells, fly research suggests

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