Stem Cell Reports recently highlighted “GABA produced by multiple bone marrow cell types regulates hematopoietic stem and progenitor cells” as their cover story. This research was conducted by SCRMC member and assistant professor of Cell and Regenerative Biology, Owen Tamplin, PhD, and members of his lab. Dr. Tamplin shares a brief description of the research below, but to learn more visit Stem Cell Reports.
How blood stem cells are regulated in the bone marrow microenvironment is still poorly understood. It is critical to understand these mechanisms because blood stem cells are used in transplants to cure many blood cancers and diseases. Therefore, we sought to investigate the role of a metabolite produced in the bone marrow that regulates blood stem cells.
We previously showed that blood stem cells have a receptor to detect the gamma-aminobutyric acid or GABA metabolite that is commonly known as a neurotransmitter in the nervous system. In our current study, we show that independent of the nervous system, bone marrow endothelial cells that make up blood vessel walls, and white blood cells (specifically B cells), produce GABA themselves.
We used genetic tools to delete the enzymes that make GABA only in endothelial and blood cells. We found that the lower GABA levels in the bone marrow of these genetic mutants signaled for blood stem cells to stop proliferating and instead increase their differentiation into B cells. We think this is a regulatory feedback loop in the bone marrow that balances blood stem cell proliferation with the need to produce more B cells. We hope that this mechanism can be targeted to improve recovery and function of the blood system after transplantation.