title: Generation of Humanized Mice for Analysis of Human Dendritic Cells.
abstract: Transplantation of human CD34(+) hematopoietic stem and progenitor cells into severe immunocompromised newborn mice allows the development of a human hemato-lymphoid system (HHLS) including dendritic cells (DCs) in vivo. Therefore, it can be a powerful tool to study human DC subsets, residing in different lymphoid and nonlymphoid organs. We have recently generated novel mouse strains called human cytokine knock-in mice in which human versions of several cytokines are knocked into Rag2(-/-)γC(-/-) strains. In addition, human SIRPα, which is a critical factor to prevent donor cell to be eliminated by host macrophages, is expressed as transgene. These mice efficiently support human myeloid cell development and, indeed, allow the analysis of three major subsets of human DC lineages, plasmacytoid DCs and CD1c(+) and CD141(+) classical DCs. Moreover, these strains also support cytokine-mobilized peripheral blood CD34(+) cell engraftment and subsequent DC development. Here we describe our standard methods to characterize DCs developed in human cytokine knock-in mice.
authors.affiliation: Division of Hematology, University Hospital Zurich, Rämistrasse 100, Zurich, CH-8006, Switzerland. ysaito@med.kobe-u.ac.jp.|Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. ysaito@med.kobe-u.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Hematology, University Hospital Zurich, Rämistrasse 100, Zurich, CH-8006, Switzerland.
authors.forename: Jana M
authors.initials: JM
authors.lastname: Ellegast
authors.affiliation: Division of Hematology, University Hospital Zurich, Rämistrasse 100, Zurich, CH-8006, Switzerland.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques; D006023:Glycoproteins / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018180:Thrombomodulin
chemical_list: D018949:Antigens, CD1; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D000954:Antigens, Surface; C437944:CD1C protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; D006023:Glycoproteins; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; C546931:THBD protein, human; D018180:Thrombomodulin
keywords: CD34+ hematopoietic stem and progenitor cell; Human dendritic cells; Humanized mouse; Stem cell transplantation