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In the medicine of the future, stem cells promise to regenerate organs in the diseased body. They might, for example, help repair a malfunctioning heart muscle or replace the brain cells lost to stroke or Parkinson’s disease. But to turn this vision into reality, simply injecting stem cells into the damaged body organ is not enough. The cells must be introduced in a manner that allows them to survive and to function properly, so that they can lead to a cure.
Crucial for stem cell function is a supporting environment called “the niche,” which is attached to the stem cell and serves as its home base. The niche protects the stem cell and controls its development, ensuring that it differentiates into a specialized cell type only when the time is right. In fact, the stem cell and its niche function together, as a single unit. In a new study published in the journal PLoS Biology, Weizmann Institute scientists have shown how such units are formed in larvae of fruit flies. The research was performed in the laboratory of Dr. Lilach Gilboa of the Biological Regulation Department by postdoctoral fellow Dr. Dana Gancz and graduate student Tamar Lengil.
In the developing embryo, the establishment of germ-line stem cells – which will continually give rise to eggs in the adult female – must be coordinated with the production of the niches, so that each stem cell has a niche. But how and when does such coordination occur?
Working with the ovaries of fruit fly larvae, the Weizmann scientists have discovered an ingenious method nature uses to produce well-balanced stem cell units: The formation of both the stem cells and the niches is controlled by the same biochemical signal. The scientists have also shown that the signal travels along a similar route to the one that controls ovulation in humans: from the brain to a hormone-secreting gland to the ovaries.
The use of the same hormonal signal helps ensure that the entire process is perfectly orchestrated and timed. The ovary of the fruit fly larva starts out with precursor cells for both niches and germ-line stem cells.
The two populations of precursor cells multiply until the larval gland issues the hormonal signal that stimulates the formation of the niches in the ovaries. Next, when a second wave of the hormone is dispatched to the ovary, germ-line stem cells form from their precursors. In other words, the same signal first creates a “home” for the germ-line stem cell, then the “tenant” cell itself.
In fact, it is crucial that the niches be formed before the stem cells. The niches make sure these cells are properly maintained, so that the fruit fly – which has close to 20 niche-stem cell units in its ovary – can daily produce dozens of eggs for over a month.
These findings provide important new insights into the relations between stem cells and their niches. Further understanding of the molecular signals that govern the formation of stem cell units and of body organs may in the future facilitate the use of stem cells in organ regeneration.
Dr. Lilach Gilboa’s research is supported by the Leir Charitable Foundations; the Karen Siem Fellowship for Women in Science; the Helen and Martin Kimmel Institute for Stem Cell Research; and the Willner Family Center for Vascular Biology. Dr. Gilboa is the incumbent of the Skirball Chair in New Scientists.
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