title: Primitive macrophages control HSPC mobilization and definitive haematopoiesis.
abstract: In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta-gonad-mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM. Specific chemical and inducible genetic depletion of macrophages or inhibition of matrix metalloproteinases (Mmps) leads to an accumulation of HSPCs in the AGM and a decrease in the colonization of haematopoietic organs. Finally, in vivo zymography demonstrates the function of primitive macrophages in extracellular matrix degradation, which allows HSPC migration through the AGM stroma, their intravasation, leading to the colonization of haematopoietic organs and the establishment of definitive haematopoiesis.
authors: 1] CNRS UMR 5235, F-34095 Montpellier, France [2] Universite Montpellier 2, Dynamique des Interactions Membranaires Normales et Pathologiques, F-34095 Montpellier, France [3] Universite Montpellier 1, F-34000 Montpellier, France.
authors: Jana
authors: J
authors: Travnickova
authors: 1] CNRS UMR 5235, F-34095 Montpellier, France [2] Universite Montpellier 2, Dynamique des Interactions Membranaires Normales et Pathologiques, F-34095 Montpellier, France [3] Universite Montpellier 1, F-34000 Montpellier, France [4] Institut Pasteur, Unité Macrophages et Développement de l'Immunité, Département de Biologie du Développement, F-75015 Paris, France [5] CNRS, URA2578, F-75015 Paris, France.
authors: Vanessa
authors: V
authors: Tran Chau
authors: 1] INSERM UMR_S949, F-67000 Strasbourg, France [2] Universite de Strasbourg, F-67000 Strasbourg, France [3] Etablissement Français du Sang-Alsace, F-67000 Strasbourg, France.
authors: Emmanuelle
authors: E
authors: Julien
authors: Montpellier RIO Imaging, F-34396 Montpellier, France.
authors: Julio
authors: J
authors: Mateos-Langerak
authors: 1] CNRS UMR 5235, F-34095 Montpellier, France [2] Universite Montpellier 2, Dynamique des Interactions Membranaires Normales et Pathologiques, F-34095 Montpellier, France [3] Universite Montpellier 1, F-34000 Montpellier, France.
authors: Catherine
authors: C
authors: Gonzalez
authors: 1] CNRS UMR 5235, F-34095 Montpellier, France [2] Universite Montpellier 2, Dynamique des Interactions Membranaires Normales et Pathologiques, F-34095 Montpellier, France [3] Universite Montpellier 1, F-34000 Montpellier, France [4] INSERM, DIMNP, F-34095 Montpellier, France.
authors: Etienne
authors: E
authors: Lelièvre
authors: 1] CNRS UMR 5235, F-34095 Montpellier, France [2] Universite Montpellier 2, Dynamique des Interactions Membranaires Normales et Pathologiques, F-34095 Montpellier, France [3] Universite Montpellier 1, F-34000 Montpellier, France.
authors: Georges
authors: G
authors: Lutfalla
authors: 1] INSERM UMR_S949, F-67000 Strasbourg, France [2] Universite de Strasbourg, F-67000 Strasbourg, France [3] Etablissement Français du Sang-Alsace, F-67000 Strasbourg, France.
authors: Manuela
authors: M
authors: Tavian
authors: 1] CNRS UMR 5235, F-34095 Montpellier, France [2] Universite Montpellier 2, Dynamique des Interactions Membranaires Normales et Pathologiques, F-34095 Montpellier, France [3] Universite Montpellier 1, F-34000 Montpellier, France [4] INSERM, DIMNP, F-34095 Montpellier, France.
authors: Karima
authors: K
authors: Kissa
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000196:embryology*; D019070:Cell Lineage; D015509:Developmental Biology; D005109:Extracellular Matrix / Q000378:metabolism; D006066:Gonads / Q000196:embryology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008650:Mesonephros / Q000196:embryology; D008856:Microscopy, Fluorescence; D013234:Stem Cells / Q000166:cytology*; D015027:Zebrafish
chemical_list: C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9