Master switches for adult blood stem cells 8/2/07. By the Johns Hopkins Kimmel Cancer Center A set of 'master switches' keeps adult blood-forming stem cells in their primitive state.

Scientists at Johns Hopkins Kimmel Cancer Center located the control switches not at the gene level, but farther down the protein production line in more recently discovered forms of ribonucleic acid (RNA). MicroRNA molecules are now known to switch off activity of the larger RNA strands that are used for the assembly of proteins.

"Stem cells are poised to make proteins essential for maturing into blood cells, but microRNAs keep them locked in their place," said Curt Civin, who led the study. The research was published the Proceedings of the National Academy of Sciences.

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To halt protein assembly, microRNAs pair up with matching full-length RNA, then fold and twist it, rendering the larger RNA useless. But the RNA pairings are not perfect, and one microRNA can latch on to several hundred RNA strands. "They act like a single circuit breaker to efficiently control hundreds of RNAs," said Civin.

"We're looking for ways to flip these microRNA switches, to control when stem cells grow into new blood cells," said Robert Georgantas, first author of the study. Unlocking the switches' code may one day enable scientists to grow new blood cells for transplant into patients with cancer and other bone marrow disorders.

To identify the key microRNAs, Georgantas sifted through thousands of RNA pieces with a custom-built, computer software program. Its algorithms let the software, fed data from samples of blood and bone marrow from healthy donors, match RNA pairs. The outcome was a core set of 33 microRNAs that match with more than 1200 of the larger variety RNA already known to be important for stem-cell maturation.

The first microRNA tested was predicted to stop stem cells from developing into red and white blood cells. As expected, stem cells without the microRNA matured, while stem cells with it matured into far fewer red and white cells.

"Using microRNAs to stall an adult blood stem cell in its early stage could help us grow new ones in test tubes, and perhaps give us more insight into stem-cell maturation for other tissue types," says Civin.

Adapted from a news release by Johns Hopkins Kimmel Cancer Center.

Image: Human neural stem cells, courtesy of Yirui Sun

Further reading

Georgantas RW 3rd, et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2750-5. Epub 2007 Feb 9. Full text