Kit regulates HSC engraftment across the human-mouse species barrier

Cell Stem Cell. 2014 Aug 7;15(2):227-38. doi: 10.1016/j.stem.2014.06.001. Epub 2014 Jul 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Crosses, Genetic
  • Enzyme-Linked Immunosorbent Assay
  • Fetal Blood / cytology
  • Gene Expression Regulation*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Lymphocytes / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation*
  • RNA, Messenger / metabolism
  • Species Specificity
  • Stem Cell Factor / metabolism*
  • Thymocytes / cytology
  • Time Factors


  • RNA, Messenger
  • Stem Cell Factor