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Tracing the origin of mast cells

August 16, 2018

Mast cells originate from two distinct sites during embryonic development

Immunology

Aug 16, 2018

Tracing the origin of mast cells

Mast cells originate from two distinct sites during embryonic development

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A peritoneal cavity mast cell (left) and a skin mast cell (right).

A peritoneal cavity mast cell (left) and a skin mast cell (right).

© Dr. Rasha Msallam, SIgN

Mast cells, a type of white blood cells involved in immunity and found mainly in tissues as opposed to the bloodstream, arise from a membrane that surrounds a mouse embryo as well as the embryo itself, a Singaporean-French team has shown.  

In the developing embryo, blood cells, both red and white, arise from cells in special regions known as hemogenic endothelia.  There are two key regions: one in the embryo itself, within the aorta-gonado-mesonephros, or AGM — a region that eventually develops into the dorsal aorta, the testis or ovary, and one in a membrane surrounding the embryo, called the yolk sac. The team, led by Marc Bajénoff from the Centre d'Immunologie de Marseille Luminy (CIML), France, in collaboration with Florent Ginhoux's group at A*STAR's Singapore Immunology Network, wanted to understand the fate of cells derived from the two different regions.    

“First we established a way to specifically label cells from the two different hemogenic endothelia so we could follow their progeny,” said Ginhoux.

They did this by developing a new genetic marker specific for all hemogenic endothelium cells, which was invisible until ‘switched on’ by a dose of the drug tamoxifen. From that point onwards all marked cells fluoresced, making them and their progeny visible. 

As the yolk sac hemogenic endothelium was present on day seven of embryonic development, but gone by day 10.5, the team could tag cells deriving from a specific source by appropriately timing the tamoxifen dose. 

Examining the embryos as they developed, they were surprised to find that many tagged cells in the embryonic skin were mast cells that had originated from cells in the yolk sac.

However, by the time of birth, almost all the skin mast cells had been replaced by new cells derived from the AGM. 

“Mast cells are important players in innate immunity — especially in the skin. In the adult they are early sentinels, and help neutralize toxins such as bee and snake venom.  They are also activated by Immunoglobulin E antibodies and involved in allergy,” said Ginhoux. 

The mast cells from the two origins had distinct characteristics and differences in gene expression, suggesting they might have varied functions.  

“The skin of the developing embryo is surrounded by amniotic fluid — it’s a very different environment from adult skin — so the mast cells probably have different functions in the embryo,” said Ginhoux.

Finally, they showed that mast cells in adult mouse skin are not replenished from the bone marrow, contrary to established thought. How the number of mast cells is maintained in adult skin remains a mystery.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).  For more information about the team’s research, please visit Ginhoux’s webpage.

References

    1. Gentek, R., Ghigo, C., Hoeffel, G., Bulle, M. J., Msallam, R. et al. Hemogenic endothelial fate mapping reveals dual developmental origin of mast cells. Immunity 48, 1160–1171.e5.| Article