Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice

Stem Cell Reports. 2016 Oct 11;7(4):591-601. doi: 10.1016/j.stemcr.2016.08.005. Epub 2016 Sep 8.


Human erythro-megakaryopoiesis does not occur in humanized mouse models, preventing the in vivo analysis of human hematopoietic stem cell (HSC) differentiation into these lineages in a surrogate host. Here we show that stably engrafted KIT-deficient NOD/SCID Il2rg-/-KitW41/W41 (NSGW41) mice support much improved human erythropoiesis and platelet formation compared with irradiated NSG recipients. Considerable numbers of human erythroblasts and mature thrombocytes are present in the bone marrow and blood, respectively. Morphology, composition, and enucleation capacity of de novo generated human erythroblasts in NSGW41 mice are comparable with those in human bone marrow. Overexpression of human erythropoietin showed no further improvement in human erythrocyte output, but depletion of macrophages led to the appearance of human erythrocytes in the blood. Human erythropoiesis up to normoblasts and platelet formation is fully supported in NSGW41 mice, allowing the analysis of human HSC differentiation into these lineages, the exploration of certain pathophysiologies, and the evaluation of gene therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cord Blood Stem Cell Transplantation
  • Erythroblasts / cytology
  • Erythroblasts / metabolism
  • Erythropoiesis / genetics*
  • Erythropoietin / genetics
  • Erythropoietin / pharmacology
  • Gene Expression
  • Graft Survival
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Heterografts
  • Humans
  • Interleukin Receptor Common gamma Subunit / deficiency
  • Interleukin Receptor Common gamma Subunit / genetics
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-kit / deficiency
  • Proto-Oncogene Proteins c-kit / genetics
  • Thrombopoiesis / genetics*


  • Interleukin Receptor Common gamma Subunit
  • Erythropoietin
  • Proto-Oncogene Proteins c-kit