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. 2019 Jul;104(7):e284-e287.
doi: 10.3324/haematol.2018.202143. Epub 2019 Jan 24.

Bone marrow niches of germline FANCC/FANCG deficient mice enable efficient and durable engraftment of hematopoietic stem cells after transplantation

Ji Zha  1 , Lori Kunselman  1 , Jian-Meng Fan  1 , Timothy S Olson  2   3   4
Affiliations

Bone marrow niches of germline FANCC/FANCG deficient mice enable efficient and durable engraftment of hematopoietic stem cells after transplantation

Ji Zha et al. Haematologica. 2019 Jul.
No abstract available

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Figures

Figure 1.
Figure 1.
Mice with germline deficiency of Fancc and/or Fancg display normal peripheral blood counts, bone marrow (BM) cellularity and hematopoietic stem/progenitor cell frequencies. (A) Complete blood count (CBC) analysis of white blood cells (WBC), neutrophils, hemoglobin and platelets in WT, Fancc−/−, Fancg−/− and Fancc−/−;Fancg−/− mice. Mean±Standard Deviation (SD). N=4-8 mice per group. (B) Hematoxylin & Eosin staining of BM section from a 6-month old wild-type (WT) and Fancc−/−;Fancg−/− double mutant mouse. (C) Total number of BM cells in 6-10-month old WT, Fancc−/−, Fancg−/− and Fancc−/−;Fancg−/− mice (mean±SD). N=4 mice per group. (D) Frequencies of LSK (Lin−Sca-1+c-Kit+), LT-HSC (Lin−Sca-1+c-Kit+CD48−CD150+), ST-HSC(c-Kit+Lin−Sca-1+CD135− CD34+), multipotent progenitor (MPP, Lin−Sca-1+c-Kit+CD135+), common myeloid progenitor (CMP, Lin−Sca-1-c-Kit+CD34+) and common lymphoid progenitor (CLP, Lin−Sca-1+c-Kit+CD127+) in 6-10-month old WT, Fancc−/−-, Fancg−/− and Fancc−/−; Fancg−/− mice, expressed as the percentage of total BM cells (mean±SD). N=3-4 mice per group). (E) Total numbers of colony-forming units (CFU) per 104 BM cells from WT and Fancc−/−;Fancg−/− mice (mean±SD). N=4 mice per group. *P<0.05 compared with WT.
Figure 2.
Figure 2.
Fancc−/−;Fancg−/− double mutant mice display no reduction in the efficiency of long-term (LT)-hematopoietic stem cell (HSC) engraftment after HSC transplantation (HSCT) compared to wild-type (WT) controls, but show enhanced early hematopoietic progenitor engraftment. (A) Primary Fanconi anemia (FA) or WT recipients were transplanted with 5x106 whole bone marrow (BM) cells from H2K-GFP donor mice after receiving 1125cGy total body irradiation (TBI). The efficiency of GFP+ donor engraftment was assessed at three weeks after 1ry BM transplantation (BMT) using competitive secondary transplantation assay, in which equal volumes (20% of cumulative BM volume from bilateral hindleg bones) of whole BM from FA or WT 1ry recipients was transplanted with 105 whole BM cells from unirradiated WT competitor mice into irradiated WT 2nd recipients. (B) Total BM cell number of Fancc−/−, Fancg−/−, Fancc−/−;Fancg−/− and WT 1ry recipients at three weeks after 1ry BMT. (C) Donor engraftment of early hematopoietic progenitors in WT and FA 1ry recipients examined by GFP+ cell percentage in platelets (PLT), Gr1 myeloid cells and B220+ B cells in 2ry recipient mice at three weeks post 2ry BMT. (D) Assessment of donor HSC engraftment in WT and FA primary recipients by GFP+ cell percentage in multiple mature blood lineage including red blood cells (RBC), PLT, Gr1+ myeloid cells, B220+ B cells and CD3+ T cells in 2ry recipient mice up to 27 weeks after 2ry BMT. (E) GFP+ reconstitution in the populations of LSK (Lin−Sca-1+ c-Kit+ ) and LT-HSC(Lin−Sca-1+c-Kit+CD48−CD150+) in the BM of 2nd recipient mice at 27 weeks after 2nd BMT. *P<0.05; **P<0.01; ***P<0.001 compared with WT.
Figure 3.
Figure 3.
Mice with germline deficiency of FANCC and/or FANCG have durable hematopoietic stem cell (HSC) engraftment after transplantation. (A) Primary wild-type (WT) and Fanconi anemia (FA) recipients were transplanted with 5x106 whole bone marrow (BM) cells from H2K-GFP donor mice after receiving 800 cGy total body irradiation (TBI). Durability of GFP+ donor engraftment was assessed at five months after 1ry BM transplantation (BMT) by competitive secondary transplantation assay, in which 106 from each FA or WT 1ry recipients were transplanted with 5x105 whole BM cells from unirradiated WT mice into irradiated (1100cGy) WT 2ry recipients. (B) The BM of 1ry mice recipients were analyzed at five months after 1st BMT. Scatterplots represent the cell cumber quantitation of total GFP+ BM, as well as GFP+ donor LSK (Lin−Sca-1+c-Kit+), Lin−Sca-1+c-Kit+CD135+ MPP, c-Kit+Lin−Sca-1+ CD135−CD34+ ST-HSC and Lin−Sca-1+ c-Kit+CD150+CD48− LT-HSC in WT, Fancc−/− and Fancc−/−;Fancg−/− recipients. *P<0.05 compared to WT. (C) Donor engraftment in primary WT, Fancc−/− and Fancc−/−;Fancg−/− recipients was assessed by GFP+ cell percentage in blood lineages including red blood cells (RBC), platelets (PLT) and Gr1+ myeloid cells in 2ry recipient mice at 3-27 weeks after 2ry BMT. *P<0.05; **P<0.01; ***P<0.001 compared with WT.
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