Well-known neurotransmitter GABA is involved in blood stem cell differentiation
GABA is the acronym for a molecule that is most famous as an inhibitory neurotransmitter. GABA and its receptor are found throughout the central nervous system and play an important role in keeping nerve networks functioning correctly. Researchers in the laboratory of institute director Irv Weissman, MD, have discovered that GABA signaling also plays a role in determining the fates of blood stem cells as they divide, and may be involved in cross-talk between the nervous system and the blood system.
“This is the first time that GABA has been shown to be involved in blood development,” said Fangfang Zhu, lead author on the paper laying out the finding in August in the Proceedings of the National Academy of Sciences. “This has never been reported before.”
Zhu, Weissman and their colleagues showed that the GABA receptor is made both the in the hematopoietic stem cell (HSC), which gives rise to all blood and immune cells, and also in a more specialized blood cell called a megakaryocyte progenitor cell.
“When data reveals something you never even considered, you should change your pre-set opinions and explore the unexpected ‘ said Weissman, senior author on the study. “Here we asked a bioinformatic question—are there genes relatively restricted to expression in blood forming stem and progenitor cells, and found that a neurotransmitter receptor—GABA-RA—was unexpectedly expressed on blood stem cells and the progenitor in bone marrow restricted to make platelets,” which are cells important in blood clotting.
“This search validated the protein as a cell surface receptor, and showed it responded to the GABA neurotransmitter by tuning up the number of platelets made, and blocking it caused the number of platelets produced to be reduced” he said. “Now we need to find out which cells make the GABA, where are they located, and can this open the door to understand how blood forming cells turn on this brain receptor? "
The researchers hope that this new information might lead to clinical advances. “Since the GABA system is so well studied, we have a real chance of being able to use this system” to have a desired effect, Zhu said. For instance, she said, it may be possible to induce blood stem cell to create more platelets in people with bleeding disorders, and fewer platelets in people with clotting disorders. Extensive blood clotting is a dangerous and significant side effect of many treatments like chemotherapy, and many disorders like sepsis.