Mature cells shown to control their stem cell parents

Researchers at Melbourne’s Walter and Eliza Hall Institute have published a study which shows that mature blood cells have the ability to communicate with and affect the behaviour of their stem cell parents.

Published in the journal Proceedings of the National Academy of Science, the study details what it refers to as a blood cell ‘feedback loop’, which the researchers say could lead to new fields of inquiry in the fight against diseases caused by disorders of stem cells.

The study was led by three WEHI researchers, Dr Carolyn de Graaf and Professor Doug Hilton from the Molecular Medicine division, and Professor Warren Alexander from the institute’s Cancer and Haematology division.

Professor Hilton said that the findings pointed to a hitherto unknown relationship between blood cells.

“We know that blood stem cells give rise to all the mature blood cells, but the standard assumption was that external factors control blood cell production and the two populations exist in isolation,” he said.

“This study shows that the mature cells actually communicate back to the stem cells, changing their gene expression and influencing their behavior.”

The upshot is that it appears blood cell disorders can disrupt the feedback loop, with profound consequences for blood stem cells.

The discovery was made while the researchers were studying what happens in animal models where there is an absence of Myb, which is a transcription factor that represses platelet (cell fragments without a nucleus containing DNA) production.

Dr de Graaf noted that the loss of the Myb gene resulted in the animals developing a high platelet blood-count, and that this in turn altered the signaling pathways that control stem cell maintenance.

“The stem cells, rather than being maintained in a ‘resting state’ until needed, were being told to continually cycle and produce mature blood cells,” Dr de Graaf said. “The stem cells were eventually exhausted and blood disorders developed because there were not enough stem cells to produce new red and white blood cells.”

The team used new generation genomic technologies to identify gene signatures in the blood stem cells that were caused by the defective signaling. It is now hoped that these gene signatures could help to improve diagnosis and treatment of various diseases.

“If we can understand the genes important for stem cell maintenance and blood cell production, then we can start to look at ways of improving transplantation techniques and therapies for blood disorders,” Dr de Graaf said.

Professor Hilton added the study also gives hope to patients who have experienced stem cell failures.

“What we would like to do is to determine whether some of these stem cell failures are due to miscommunication between mature blood cells and stem cells, with the possibility of finding new ways to treat these disorders down the track,” he said.

The research was conducted with the help of funding from the National Health and Medical Research Council, the National Heart, Lung, and Blood Institute, the Cancer Council Victoria, the Australian Cancer Research Foundation, Murigen Pty Ltd and the Australian Stem Cell Centre.