The GABA receptor GABRR1 is expressed on and functional in hematopoietic stem cells and megakaryocyte progenitors.

Publication Type	Academic Article
Authors	Zhu F, Feng M, Sinha R, Murphy M, Luo F, Kao K, Szade K, Seita J, Weissman I
Journal	Proc Natl Acad Sci U S A
Volume	116
Issue	37
Pagination	18416-18422
Date Published	08/26/2019
ISSN	1091-6490
Keywords	Hematopoietic Stem Cells, Megakaryocyte Progenitor Cells, Receptors, GABA-A
Abstract	GABRR1 is a rho subunit receptor of GABA, the major inhibitory neurotransmitter in the mammalian brain. While most investigations of its function focused on the nervous system, its regulatory role in hematopoiesis has not been reported. In this study, we found GABRR1 is mainly expressed on subsets of human and mouse hematopoietic stem cells (HSCs) and megakaryocyte progenitors (MkPs). GABRR1-negative (GR-) HSCs led to higher donor-derived hematopoietic chimerism than GABRR1-positive (GR+) HSCs. GR+ but not GR- HSCs and MkPs respond to GABA in patch clamp studies. Inhibition of GABRR1 via genetic knockout or antagonists inhibited MkP differentiation and reduced platelet numbers in blood. Overexpression of GABRR1 or treatment with agonists significantly promoted MkP generation and megakaryocyte colonies. Thus, this study identifies a link between the neural and hematopoietic systems and opens up the possibility of manipulating GABA signaling for platelet-required clinical applications.
DOI	10.1073/pnas.1906251116
PubMed ID	31451629
PubMed Central ID	PMC6744911