title: Depletion of Neural Crest-Derived Cells Leads to Reduction in Plasma Noradrenaline and Alters B Lymphopoiesis.
abstract: Hematopoietic stem cells and their lymphoid progenitors are supported by the bone marrow (BM) microenvironmental niches composed of various stromal cells and Schwann cells and sympathetic nerve fibers. Although neural crest (NC) cells contribute to the development of all the three, their function in BM is not well understood. In this study, NC-derived cells were ablated with diphtheria toxin in double-transgenic mice expressing NC-specific Cre and Cre-driven diphtheria toxin receptor with yellow fluorescent protein reporter. We found that yellow fluorescent protein-expressing, NC-derived nonhematopoietic cells in BM expressed hematopoietic factors Cxcl12 and stem cell factor The ablation of NC-derived cells led to a significant decrease in B cell progenitors but not in hematopoietic stem cells or myeloid lineage cells in BM. Interestingly, plasma noradrenaline was markedly decreased in these mice. The i.p. administration of 6-hydroxydopamine, a known neurotoxin for noradrenergic neurons, led to a similar phenotype, whereas the administration of a noradrenaline precursor in NC-ablated mice partially rescued this phenotype. Additionally, the continuous administration of adrenergic receptor β antagonists partially decreased the number of B cell progenitors while preserving B lymphopoiesis in vitro. Taken together, our results indicate that NC-derived cell depletion leads to abnormal B lymphopoiesis partially through decreased plasma noradrenaline, suggesting this as a novel mechanism regulated by molecules released by the sympathetic neurons.
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; and.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsunokuma
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; and.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; and.
authors.forename: Chiaki
authors.identifier: 0000-0002-6505-593X
authors.initials: C
authors.lastname: Matsumoto
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; and.
authors.forename: Motokazu
authors.identifier: 0000-0002-0075-5871
authors.initials: M
authors.lastname: Tsuneto
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; and.
authors.forename: Kana
authors.initials: K
authors.lastname: Isono
authors.affiliation: Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imanaka-Yoshida
authors.affiliation: Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; and yamazaki@doc.medic.mie-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology* / Q000276:immunology; D009638:Norepinephrine / Q000097:blood*; D016133:Polymerase Chain Reaction
chemical_list: D009638:Norepinephrine