title: Proinflammatory signaling regulates hematopoietic stem cell emergence.
abstract: Hematopoietic stem cells (HSCs) underlie the production of blood and immune cells for the lifetime of an organism. In vertebrate embryos, HSCs arise from the unique transdifferentiation of hemogenic endothelium comprising the floor of the dorsal aorta during a brief developmental window. To date, this process has not been replicated in vitro from pluripotent precursors, partly because the full complement of required signaling inputs remains to be determined. Here, we show that TNFR2 via TNF? activates the Notch and NF-?B signaling pathways to establish HSC fate, indicating a requirement for inflammatory signaling in HSC generation. We determine that primitive neutrophils are the major source of TNF?, assigning a role for transient innate immune cells in establishing the HSC program. These results demonstrate that proinflammatory signaling, in the absence of infection, is utilized by the developing embryo to generate the lineal precursors of the adult hematopoietic system.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 6107, La Jolla, CA 92093, USA; Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Campus Universitario de Espinardo, Murcia 30100, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Espín-Palazón
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 6107, La Jolla, CA 92093, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Stachura
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 6107, La Jolla, CA 92093, USA.
authors.forename: Clyde A
authors.initials: CA
authors.lastname: Campbell
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Campus Universitario de Espinardo, Murcia 30100, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: García-Moreno
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 6107, La Jolla, CA 92093, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Del Cid
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 6107, La Jolla, CA 92093, USA.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Kim
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Campus Universitario de Espinardo, Murcia 30100, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Candel
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Campus Universitario de Espinardo, Murcia 30100, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Meseguer
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Campus Universitario de Espinardo, Murcia 30100, Spain. Electronic address: vmulero@um.es.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Natural Sciences Building 6107, La Jolla, CA 92093, USA; Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: dtraver@ucsd.edu.
authors.forename: David
authors.initials: D
authors.lastname: Traver
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D051880:Receptors, Notch; D014409:Tumor Necrosis Factor-alpha