title: Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation.
abstract: In recent years, advances in the humanized mouse system have led to significantly increased levels of human hematopoietic stem cell (HSC) engraftment. The remaining limitations in human HSC engraftment and function include lymphoid-skewed differentiation and inefficient myeloid development in the recipients. Limited human HSC function may partially be attributed to the inability of the host mouse microenvironment to provide sufficient support to human hematopoiesis. To address this problem, we created membrane-bound human stem cell factor (SCF)/KIT ligand (KL)-expressing NOD/SCID/IL2rgKO (hSCF Tg NSG) mice. hSCF Tg NSG recipients of human HSCs showed higher levels of both human CD45(+) cell engraftment and human CD45(+)CD33(+) myeloid development compared with NSG recipients. Expression of hSCF/hKL accelerated the differentiation of the human granulocyte lineage cells in the recipient bone marrow. Human mast cells were identified in bone marrow, spleen, and gastrointestinal tissues of the hSCF Tg NSG recipients. This novel in vivo humanized mouse model demonstrates the essential role of membrane-bound hSCF in human myeloid development. Moreover, the hSCF Tg NSG humanized recipients may facilitate investigation of in vivo differentiation, migration, function, and pathology of human mast cells.
authors.affiliation: Research Unit for Human Disease Models, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Takagi
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hijikata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takanori
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Shinobu
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008407:Mast Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D019089:Stem Cell Factor / Q000378:metabolism*; D018183:Transplantation Chimera / Q000502:physiology; D023001:Transplantation Tolerance / Q000502:physiology
chemical_list: D019089:Stem Cell Factor