Berger, AlexandraFrelin, CatherineShah, Divya K.Benveniste, PatriciaHerrington, RobertGerard, NormaZúñiga-Pflücker, Juan-CarlosIscove, Norman N.Paige, Christopher J.2013-06-052013Berger, Alexandra, Catherine Frelin, Divya K. Shah, Patricia Benveniste, Robert Herrington, Norma P. Gerard, Juan-Carlos Zúñiga-Pflücker, Norman N. Iscove, and Christopher J. Paige. 2013. Neurokinin-1 receptor signalling impacts bone marrow repopulation efficiency. PLoS ONE 8(3): e58787.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10718380Tachykinins are a large group of neuropeptides with both central and peripheral activity. Despite the increasing number of studies reporting a growth supportive effect of tachykinin peptides in various in vitro stem cell systems, it remains unclear whether these findings are applicable in vivo. To determine how neurokinin-1 receptor (NK-1R) deficient hematopoietic stem cells would behave in a normal in vivo environment, we tested their reconstitution efficiency using competitive bone marrow repopulation assays. We show here that bone marrow taken from NK-1R deficient mice (Tacr1−/−) showed lineage specific B and T cell engraftment deficits compared to wild-type competitor bone marrow cells, providing evidence for an involvement of NK-1R signalling in adult hematopoiesis. Tachykinin knockout mice lacking the peptides SP and/or HK-1 (Tac1−/−, Tac4−/− and Tac1−/−/Tac4−/− mice) repopulated a lethally irradiated wild-type host with similar efficiency as competing wild-type bone marrow. The difference between peptide and receptor deficient mice indicates a paracrine and/or endocrine mechanism of action rather than autocrine signalling, as tachykinin peptides are supplied by the host environment.en-USBiologyBiochemistryNeurochemistryNeurochemicalsNeuropeptidesDevelopmental BiologyStem CellsHematopoietic Stem CellsModel OrganismsAnimal ModelsMouseMolecular Cell BiologyCellular TypesHematopoietic Progenitor CellsMedicineClinical Research DesignAnimal Models of DiseaseJournal Article2013-06-0510.1371/journal.pone.0058787