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Vitamin A deficiency is detrimental to blood stem cells

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Many specialized cells such as those in the skin, gut or blood have a lifespan of only a few days. Therefore, steady replenishment of these cells is indispensable. They arise from so-called "adult" stem cells that divide continuously. In addition, there is a group of very special stem cells in the bone marrow that remain in a kind of dormancy most of the time and only become active in an emergency such as bacterial or viral infections, heavy blood loss or in the wake of chemotherapy.

Once their work is done, the body sends its most potent stem cells back to sleep. Researchers assume that this protects them from dangerous mutations that may lead to leukemia.

The mechanisms that activate these special stem cells or make them go back to sleep after their work is done have remained elusive until now. Scientists have identified retinoic acid, a vitamin A metabolite, as a crucial factor in this process. If this substance is absent, active stem cells are unable to return to a dormant state and mature into specialized blood cells instead. This means that they are lost as a reservoir. This was shown in studies with specially bred mice whose dormant stem cells are green fluorescent.

"If we feed these mice on a vitamin A deficient diet for some time, this leads to a loss of the stem cells," said Nina Cabezas-Wallscheid, Ph.D., first author of the study that appeared recently in Cell and a member of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "Thus, we can prove for the first time that vitamin A has a direct impact on blood stem cells."

This finding not only enhances our understanding of the development of blood cells, it also sheds new light on prior studies that demonstrate that vitamin A deficiency impairs the immune system.

"This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet," Dr. Cabezas-Wallscheid emphasized. The body cannot produce its own vitamin A.

The scientists also have hopes for new prospects in cancer treatment. There is evidence that cancer cells, like healthy stem cells, also rest in a state of dormancy. When dormant, their metabolism is almost completely shut down and this makes them resistant to chemotherapy.

"Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables," explained Andreas Trumpp, Ph.D., a division head at the DKFZ and director of HI-STEM. "If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies."

In addition, in collaboration with colleagues from the European Bioinformatics Institute in Cambridge, the team performed genome-wide analyses of single cells and discovered that the transition from dormant to active stem cells and then on to progenitor cells is a continuous one and follows a different path for each individual cell. So far, scientists had assumed that specific cell types develop step by step in a defined pattern. This finding revolutionizes the previous concept of how cell differentiation in the body takes place.

Learn more:

http://www.dkfz.de/en/index.html
DOI: 10.1016/j.cell.2017.04.018