The behavior of naive HSCs after transplantation into a Wif1 microenvironment. (A) Schematic representation of the transplantation study. (B) HSCs reconstitute Wif1 mice at significantly higher levels than control OB hosts at low doses. A total of 50, 100, or 200 LSKCD34⁻ HSCs from CD45.1 SJL BM were transplanted together with 2 × 10⁵ congenic CD45.2 BM cells from C57Bl/6 mice into lethally irradiated control OB or Wif1 recipients. Data are represented as the percentage of CD45.1⁺ cells ± SD in the myeloid, T, and B peripheral blood cells, 12 weeks after transplantation (n = 4 or 5, P = .03 at a cell dose of 50). (C) HSCs have a compromised self-renewal potential in secondary wild-type hosts after primary transplant into Wif1 hosts. A total of 500, 1000, or 2000 sorted CD45.1⁺ donor LSK cells from primary OB or Wif1 recipients were transplanted into lethally irradiated congenic C57Bl/6 recipients. Results are percentage of CD45.1⁺ cells in B, T, and myeloid peripheral blood cells in each individual mouse at 19 weeks after secondary transplantation. Significance was determined by a 2-tailed t test: 500 cells, P = .006; 1000 cells, P = .044; and 2000 cells, P = .049.