Fetal monocytes and the origins of tissue-resident macrophages. 2018

Guillaume Hoeffel, and Florent Ginhoux
Aix-Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille-Luminy (CIML), Marseille, France. Electronic address: hoeffel@ciml.univ-mrs.fr.

Tissue-resident macrophages have pivotal functions for tissue defense and homeostasis. Two main discoveries have changed our current understanding of macrophage development: Their embryonic origin and their ability to self-renew throughout the lifespan. It is now well accepted that most tissue-resident macrophages are long-lived cells derived from a transient hematopoietic wave of erythro-myeloid progenitors (EMPs) emerging in the yolk sac. At least two distinct pathways derived from EMPs have been implicated in macrophage development. The first one, c-Myb-independent is giving rise to yolk sac macrophages also called primitive macrophages, and bypassing the classical monocytic intermediates. The second requires c-Myb expression and start once EMPs seed the fetal liver where they generate fetal monocytes. Sequentially, primitive macrophages seed every tissue and will ultimately give rise to microglia in the brain, rapidly isolated by the blood brain barrier, while EMP-derived fetal monocytes infiltrate every other tissues and gradually generate the major pool of adult tissue-resident macrophages by diluting the initial primitive macrophage contribution. A third wave of hematopoietic stem cells (HSC)-derived monocytes is also emerging from the fetal liver to contribute to the long-lived macrophage pool established at birth while the adult hematopoiesis is only starting in the bone marrow. We propose here to review recent insights about the different embryonic hematopoietic programs responsible for the generation of long-lived tissue-resident macrophages and their maintenance after birth.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D005260 Female Females
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015017 Yolk Sac The first of four extra-embryonic membranes to form during EMBRYOGENESIS. In REPTILES and BIRDS, it arises from endoderm and mesoderm to incorporate the EGG YOLK into the DIGESTIVE TRACT for nourishing the embryo. In placental MAMMALS, its nutritional function is vestigial; however, it is the source of INTESTINAL MUCOSA; BLOOD CELLS; and GERM CELLS. It is sometimes called the vitelline sac, which should not be confused with the VITELLINE MEMBRANE of the egg. Vitelline Sac of Embryo,Embryo Vitelline Sac,Embryo Vitelline Sacs,Sac, Yolk,Sacs, Yolk,Yolk Sacs
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D019070 Cell Lineage The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo. Cell Lineages,Lineage, Cell,Lineages, Cell

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