Dual cholinergic signals regulate daily migration of hematopoietic stem cells and leukocytes

Andrés García-García, Claudia Korn, María García-Fernández, Olivia Domingues, Javier Villadiego, Daniel Martín-Pérez, Joan Isern, José A. Bejarano-García, Jacques Zimmer, José A. Pérez-Simón, Juan J. Toledo-Aral, Tatiana Michel, Matti S. Airaksinen, Simón Méndez-Ferrer

Research output: Contribution to journalArticleResearchpeer-review

67 Citations (Scopus)


Hematopoietic stem and progenitor cells (HSPCs) and leukocytes circulate between the bone marrow (BM) and peripheral blood following circadian oscillations. Autonomic sympathetic noradrenergic signals have been shown to regulate HSPC and leukocyte trafficking, but the role of the cholinergic branch has remained unexplored. We have investigated the role of the cholinergic nervous system in the regulation of day/night traffic of HSPCs and leukocytes in mice. We show here that the autonomic cholinergic nervous system (including parasympathetic and sympathetic) dually regulates daily migration of HSPCs and leukocytes. At night, central parasympathetic cholinergic signals dampen sympathetic noradrenergic tone and decrease BM egress of HSPCs and leukocytes. However, during the daytime, derepressed sympathetic noradrenergic activity causes predominant BM egress of HSPCs and leukocytes via b3–adrenergic receptor. This egress is locally supported by light-triggered sympathetic cholinergic activity, which inhibits BM vascular cell adhesion and homing. In summary, central (parasympathetic) and local (sympathetic) cholinergic signals regulate day/night oscillations of circulating HSPCs and leukocytes. This study shows how both branches of the autonomic nervous system cooperate to orchestrate daily traffic of HSPCs and leukocytes.

Original languageEnglish
Pages (from-to)224-236
Number of pages13
Issue number3
Publication statusPublished - 17 Jan 2019


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