title: Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human.
abstract: Understanding of natural killer (NK) cell development in human is incomplete partly because of limited access to appropriate human tissues. We have developed a cytokine-enhanced humanized mouse model with greatly improved reconstitution and function of human NK cells. Here we report the presence of a cell population in the bone marrow of the cytokine-treated humanized mice that express both NK cell marker CD56 and myeloid markers such as CD36 and CD33. The CD56(+)CD33(+)CD36(+) cells are also found in human cord blood, fetal and adult bone marrow. Although the CD56(+)CD33(+)CD36(+) cells do not express the common NK cell functional receptors and exhibit little cytotoxic and cytokine-producing activities, they readily differentiate into mature NK cells by acquiring expression of NK cell receptors and losing expression of the myeloid markers. Further studies show that CD33(+)CD36(+) myeloid NK precursors are derived from granulo-myelomonocytic progenitors. These results delineate the pathway of human NK cell differentiation from myeloid progenitors in the bone marrow and suggest the utility of humanized mice for studying human hematopoiesis.
authors.affiliation: Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 138673, Singapore.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, 138602, Singapore.|School of Biological Sciences, Nanyang Technological University of Singapore, 637551, Singapore.
authors.forename: Weijian
authors.initials: W
authors.lastname: Ye
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, 138602, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Jian Tan
authors.affiliation: Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 138673, Singapore.
authors.forename: Kylie Su
authors.initials: KS
authors.lastname: Mei Yong
authors.affiliation: Humanized Mouse Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 138673, Singapore.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Obstetrics &Gynaecology, KK Women's and Children's Hospital, 229899, Singapore.
authors.forename: Shu
authors.initials: S
authors.lastname: Qi Tan
authors.affiliation: Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, 229899, Singapore.
authors.forename: Eva
authors.initials: E
authors.lastname: Loh
authors.affiliation: Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, 229899, Singapore.|Duke-NUS Graduate Medical School, 169857, Singapore.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Te Chang
authors.affiliation: Department of Obstetrics &Gynaecology, KK Women's and Children's Hospital, 229899, Singapore.|Duke-NUS Graduate Medical School, 169857, Singapore.
authors.forename: Thiam
authors.initials: T
authors.lastname: Chye Tan
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, 138602, Singapore.|School of Biological Sciences, Nanyang Technological University of Singapore, 637551, Singapore.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Preiser
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, 138602, Singapore.|The Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D005333:Fetus; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology / Q000637:transplantation*; D006801:Humans; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000008:administration & dosage; D051379:Mice; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000276:immunology; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics / Q000276:immunology
chemical_list: D015415:Biomarkers; C571163:CD33 protein, human; D018955:CD36 Antigens; D019002:CD56 Antigen; C569274:IL15 protein, human; D019409:Interleukin-15; D008565:Membrane Proteins; C522918:NCAM1 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; C084881:flt3 ligand protein