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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Cosgun KN,Rahmig S,Mende N,Reinke S,Hauber I,Schäfer C,Petzold A,Weisbach H,Heidkamp G,Purbojo A,Cesnjevar R,Platz A,Bornhäuser M,Schmitz M,Dudziak D,Hauber J,Kirberg J,Waskow C

doi

10.1016/j.stem.2014.06.001

subject

Has Abstract

pub_date

2014-08-07 00:00:00

pages

227-38

issue

2

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(14)00249-5

journal_volume

15

pub_type

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