Stem Cell Defect in Ubiquitin-Green Fluorescent Protein Mice Facilitates Engraftment of Lymphoid-Primed Hematopoietic Stem Cells

Stem Cells. 2018 Aug;36(8):1237-1248. doi: 10.1002/stem.2828. Epub 2018 Apr 15.

Abstract

Transgenic mice expressing green fluorescent protein (GFP) are useful in transplantation experiments. When we used ubiquitin-GFP (UBC-GFP) transgenic mice to study the availability of niches for transplanted hematopoietic stem and progenitor cells, the results were strikingly different from the corresponding experiments that used congenic mice polymorphic in the CD45 antigen. Analysis of these unexpected results revealed that the hematopoiesis of UBC-GFP mice was outcompeted by the hematopoiesis of wild-type (WT) mice. Importantly, UBC-GFP mice engrafted the transplanted bone marrow of WT mice without conditioning. There was a significant bias toward lymphopoiesis in the WT branch of chimeric UBC-GFP/WT hematopoiesis. A fraction of immature Sca-1+ cells in the spleen of UBC-GFP mice expressed GFP at a very high level. The chimeric hematopoiesis was stable in the long term and also after transplantation to secondary recipient mice. The article thus identifies a specific defect in the hematopoiesis of UBC-GFP transgenic mice that compromises the lymphoid-primed hematopoietic stem cells in the bone marrow and spleen. Stem Cells 2018;36:1237-1248.

Keywords: Bone marrow transplantation; Cell competition; Extramedullary hematopoiesis; Green fluorescent protein; Hematopoiesis; Lymphopoiesis; Stem cell niche; Stem cells; Transgenic mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / metabolism
  • Chimera
  • Green Fluorescent Proteins / metabolism*
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / metabolism*
  • Lymphocytes / metabolism*
  • Lymphopoiesis
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spleen / metabolism
  • Splenectomy
  • Thymus Gland / metabolism
  • Ubiquitin / metabolism*

Substances

  • Ubiquitin
  • Green Fluorescent Proteins