Dopamine signaling regulates hematopoietic stem and progenitor cell function.

Hematopoietic stem and progenitor cell (HSPC) function in bone marrow (BM) is controlled by stroma-derived signals, but the identity and interplay of these signals remain incompletely understood. Here, we show that sympathetic nerve-derived dopamine directly controls HSPC behavior through D2-subfamily dopamine receptors. Blockade of dopamine synthesis as well as pharmacological or genetic inactivation of D2-subfamily dopamine receptors lead to reduced HSPC frequency, inhibition of proliferation and low BM transplantation efficiency. Conversely, treatment with a D2-type receptor agonist increases BM regeneration and transplantation efficiency. Mechanistically, dopamine controls expression of the kinase Lck, which, in turn, regulates mitogen-activated protein kinase-mediated signaling triggered by stem cell factor in HSPCs. Our work reveals critical functional roles of dopamine in HSPCs, which may open up new therapeutic options for improved BM transplantation and other conditions requiring the rapid expansion of HSPCs.