title: Kit regulates HSC engraftment across the human-mouse species barrier.
abstract: In-depth analysis of the cellular and molecular mechanisms regulating human HSC function will require a surrogate host that supports robust maintenance of transplanted human HSCs in vivo, but the currently available options are problematic. Previously we showed that mutations in the Kit receptor enhance engraftment of transplanted HSCs in the mouse. To generate an improved model for human HSC transplantation and analysis, we developed immune-deficient mouse strains containing Kit mutations. We found that mutation of the Kit receptor enables robust, uniform, sustained, and serially transplantable engraftment of human HSCs in adult mice without a requirement for irradiation conditioning. Using this model, we also showed that differential KIT expression identifies two functionally distinct subpopulations of human HSCs. Thus, we have found that the capacity of this Kit mutation to open up stem cell niches across species barriers has significant potential and broad applicability in human HSC research.
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Kadriye Nehir
authors.initials: KN
authors.lastname: Cosgun
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Rahmig
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mende
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Reinke
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Hauber
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Schäfer
authors.affiliation: Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Petzold
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Weisbach
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Dermatology, Research Module II, University Hospital of Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Hartmannstrasse 14, 91052 Erlangen, Germany.
authors.forename: Gordon
authors.initials: G
authors.lastname: Heidkamp
authors.affiliation: Department of Paediatric Cardiac Surgery, University Hospital of Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Loschgestrasse 15, 91054 Erlangen, Germany.
authors.forename: Ariawan
authors.initials: A
authors.lastname: Purbojo
authors.affiliation: Department of Paediatric Cardiac Surgery, University Hospital of Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Loschgestrasse 15, 91054 Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Cesnjevar
authors.affiliation: DKMS Lifeline Cord Blood Bank, Blasewitzer Strasse 43, 01307 Dresden, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Platz
authors.affiliation: Department of Hematology/Oncology, University Hospital, TU Dresden, Fetscherstr 74, 01307 Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Dermatology, Research Module II, University Hospital of Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Hartmannstrasse 14, 91052 Erlangen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.affiliation: Paul Ehrlich Institut, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kirberg
authors.affiliation: Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Faculty of Medicine, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Electronic address: claudia.waskow@tu-dresden.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Waskow
mesh_terms: D000818:Animals; D019070:Cell Lineage; D003433:Crosses, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D019089:Stem Cell Factor / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D019089:Stem Cell Factor