title: NACA deficiency reveals the crucial role of somite-derived stromal cells in haematopoietic niche formation.
abstract: The ontogeny of haematopoietic niches in vertebrates is essentially unknown. Here we show that the stromal cells of the caudal haematopoietic tissue (CHT), the first niche where definitive haematopoietic stem/progenitor cells (HSPCs) home in zebrafish development, derive from the caudal somites through an epithelial-mesenchymal transition (EMT). The resulting stromal cell progenitors accompany the formation of the caudal vein sinusoids, the other main component of the CHT niche, and mature into reticular cells lining and interconnecting sinusoids. We characterize a zebrafish mutant defective in definitive haematopoiesis due to a deficiency in the nascent polypeptide-associated complex alpha subunit (NACA). We demonstrate that the defect resides not in HSPCs but in the CHT niche. NACA-deficient stromal cell progenitors initially develop normally together with the sinusoids, and HSPCs home to the resulting niche, but stromal cell maturation is compromised, leading to a niche that is unable to support HSPC maintenance, expansion and differentiation.
authors.affiliation: Institut Pasteur, Department of Developmental &Stem Cell Biology, Paris 75015, France.|CNRS, URA2578, Paris 75015, France.|INSERM, Paris 75013, France.
authors.forename: Emi
authors.initials: E
authors.lastname: Murayama
authors.affiliation: Institut Pasteur, Department of Developmental &Stem Cell Biology, Paris 75015, France.|CNRS, URA2578, Paris 75015, France.
authors.forename: Milka
authors.initials: M
authors.lastname: Sarris
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 94112, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Redd
authors.affiliation: Institut Pasteur, Department of Developmental &Stem Cell Biology, Paris 75015, France.|CNRS, URA2578, Paris 75015, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Le Guyader
authors.affiliation: Institut Pasteur, Department of Developmental &Stem Cell Biology, Paris 75015, France.|CNRS, URA2578, Paris 75015, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vivier
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 94112, USA.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Horsley
authors.affiliation: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 94112, USA.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Trede
authors.affiliation: Institut Pasteur, Department of Developmental &Stem Cell Biology, Paris 75015, France.|CNRS, URA2578, Paris 75015, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Herbomel
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology*; D009154:Mutation; D019170:Somites / Q000166:cytology*; D015027:Zebrafish
chemical_list: D018832:Molecular Chaperones; C096099:nascent-polypeptide-associated complex