Kit Regulates HSC Engraftment across the Human-Mouse Species Barrier

被引：129

作者：

Cosgun, Kadriye Nehir ^{[1
]}

Rahmig, Susann ^{[1
]}

Mende, Nicole ^{[1
]}

Reinke, Soeren ^{[1
]}

Hauber, Ilona ^{[2
]}

Schaefer, Carola ^{[2
]}

Petzold, Anke ^{[3
]}

Weisbach, Henry ^{[1
]}

Heidkamp, Gordon ^{[4
]}

Purbojo, Ariawan ^{[5
]}

Cesnjevar, Robert ^{[5
]}

Platz, Alexander ^{[6
]}

Bornhaeuser, Martin ^{[7
]}

Schmitz, Marc ^{[3
]}

Dudziak, Diana ^{[4
]}

Hauber, Joachim ^{[2
]}

Kirberg, Joerg ^{[8
]}

Waskow, Claudia ^{[1
]}

机构：

[1] Tech Univ Dresden, Fac Med, Inst Immunol, D-01307 Dresden, Germany

[2] Leibniz Inst Expt Virol, Heinrich Pette Inst, D-20251 Hamburg, Germany

[3] Tech Univ Dresden, Fac Med, Inst Immunol, D-01307 Dresden, Germany

[4] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Dermatol, Lab Dendrit Cell Biol, D-91052 Erlangen, Germany

[5] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Paediat Cardiac Surg, D-91054 Erlangen, Germany

[6] DKMS Lifeline Cord Blood Bank, D-01307 Dresden, Germany

[7] Tech Univ Dresden, Univ Hosp, Dept Hematol Oncol, D-01307 Dresden, Germany

[8] Paul Ehrlich Inst, Fed Inst Vaccines & Biomed, D-63225 Langen, Germany

来源：

CELL STEM CELL | 2014年 / 15卷 / 02期

关键词：

HEMATOPOIETIC STEM-CELLS; TRANSGENIC EXPRESSION; IMMUNE-SYSTEM; CORD BLOOD; IN-VIVO; MICE; RECEPTOR; MODEL; PROGENITORS; POPULATIONS;

D O I：

10.1016/j.stem.2014.06.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：227 / 238

页数：12

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