title: Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions.
abstract: The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14(low)CD16(-) precursor to form CD14(high)CD16(+) cells without producing the CD14(high)CD16(-) cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.
authors.affiliation: Inserm, Institut Gustave Roussy, Villejuif, France.
authors.forename: Olena
authors.initials: O
authors.lastname: Klimchenko
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
authors.forename: Sofiane
authors.initials: S
authors.lastname: Hamidi
authors.forename: Paule
authors.initials: P
authors.lastname: Opolon
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: Mélanie
authors.initials: M
authors.lastname: Routhier
authors.forename: Jamel
authors.initials: J
authors.lastname: El-Benna
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Siham
authors.initials: S
authors.lastname: Boukour
authors.forename: Bernadette
authors.initials: B
authors.lastname: Lescure
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Françoise
authors.initials: F
authors.lastname: Norol
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005333:Fetus / Q000166:cytology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG