Wednesday, 10 April 2013

Hematopoietic stem cells recognise and respond to emergencies

In a new study, a collaborative team of researchers from Inserm, CNRS and MDC have discovered a previously unknown ability that hematopoietic stem cells (HSCs) have. According to the study, HSCs can recognise when the body experiences certain stress conditions, like infection or inflammation, and respond accordingly by producing the type of cell that is in highest demand. The study may one day help patients who need a hematopoietic stem cell transplant to recover faster.

In previous studies Michael Sieweke, leading author of this study, had discovered that the differentiation pathway followed by HSCs is not selected in random, instead HSCs "decide" what cells they will differentiate into under the presence of certain factors and signals from their surrounding environment.

Purpose of this study was to examine how HSCs respond under emergency conditions. For example in case of an infection, would they increase the production of cells that can combat the intruder, like macrophages and other white blood cells ? Until recently, it was widely accepted that there was no mechanism to trigger HSCs into responding to such emergency conditions. So, the obvious answer would be a simple no.

Three different blood cells, T-cell (right), a platelet in the center and a red blood cell

However, the researchers discovered that not only such a mechanism exists but it's so sophisticated that the HSCs respond by producing exactly the types of cells needed.

"We have discovered that a biological molecule produced in large quantities by the body during infection or inflammation directly shows stem cells the path to take," said Dr. Sandrine Sarrazin, co-author of the study, from the Inserm Institute.

The molecule in question is a protein called "Macrophage Colony-Stimulating Factor" (M-CSF). Sarrazin explains how it works:

"As a result of this molecule, called M-CSF the switch of the myeloid lineage (the PU.1 gene) is activated and the stem cells quickly produce the cells that are best suited to the situation such as macrophages." 

According to Sieweke, the study has the potential to help thousands of patients in need of a HSC transplant, like leukemia victims.

"Thanks to M-CSF, it may be possible to stimulate the production of useful cells while avoiding to produce those that can inadvertently attack the body of these patients. They could therefore protect against infections while their immune system is being reconstituted". said Sieweke.

Computer generated image of the M-CSF protein
Computer generated image of the M-CSF protein

Noushine Mossadegh-Keller, Sandrine Sarrazin, Prashanth K. Kandalla, Leon Espinosa, E. Richard Stanley, Stephen L. Nutt, Jordan Moore, & Michael H. Sieweke (2013). M-CSF instructs myeloid lineage fate in single haematopoietic stem cells Nature : 10.1038/nature12026

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