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Zebrafish employ cellular shield to protect blood stem cells from damaging ultraviolet light

While studying the blood stem cells that reside in the kidney of the zebrafish embryo, researchers observed that cells called melanocytes were positioned above the stem cells in an umbrella pattern, and subsequently showed this umbrella served as a shield protecting stem cells from damaging ultraviolet (UV) light. When stem cells divide, they can form more stem cells or other cells that perform specialized functions. The blood stem cell niche is crucial for regulating the process of new blood cell formation, and its location varies among species—for example, it is found in the bone marrow of adult mammals and in the kidney of the majority of fish species. Little is known about the factors (e.g., environmental) that have influenced the placement of stem cell niches in mammals and fish.

A recent report described an opportune observation that a cluster of melanocytes formed an umbrella pattern directly above the kidney stem cell niche in zebrafish. Zebrafish are an important animal model system that scientists use to better understand human physiology and disease. One distinct advantage that zebrafish embryos have are that they are “transparent” (e.g., clear)—allowing scientists to watch the fertilized eggs grow into fully formed baby fish under a microscope. Previous research has shown that the melanocyte is a cell in human skin that produces and contains the pigment melanin; melanin protects skin cells from DNA damage caused by UV light.

This led the research team to hypothesize that melanocytes may serve as a shield to protect the blood stem cells in the zebrafish kidney from damaging UV light. They tested this hypothesis by studying a mutant form of zebrafish embryo that lacks melanocytes. After UV-light exposure, stem cells from mutant zebrafish embryos contained significantly more DNA damage compared to stem cells from normal zebrafish embryos with melanocytes. Furthermore, mutant zebrafish embryos showed a significant decrease in stem cell numbers compared to those in normal embryos. These findings suggest that the melanocytes were protecting the stem cell niche from damaging UV light. The researchers then sought to determine whether it was the “orientation” of the melanocyte umbrella that played a protective role. When anesthetized, zebrafish embryos flip upside-down—this change in orientation no longer positions the melanocyte umbrella between the UV light and kidney stem cell niche. Under these conditions, stem cell numbers in normal zebrafish were reduced to the same level as those in mutant embryos after UV treatment. These findings confirm that the orientation of the melanocyte umbrella is critical to protect stem cells from UV damage and suggests that melanocytes form an optical shield.

The research team also showed that other types of fish contain a melanocyte shield and postulated that land-based animals such as mammals employ a “bone” shield to protect the blood stem cell niche in the bone marrow from damaging UV light. These new findings suggest that protection against damage from UV light plays an important role in influencing the placement of animals’ stem cell niche.

References

Kapp FG, Perlin JR, Hagedorn EJ,…Zon LI. Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 558: 445-448, doi: 10.1038/s41586-018-0213-0, 2018.

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