k-n, GFP was not detected in bone-lining osteoblast lineage cells (Osteopontin) in the diaphysis ( k-m) or in trabecular bone ( n). Endothelial cells were stained with an anti- Endoglin antibody. h-j, GFP was primarily expressed by perivascular cells in the bone marrow of Scf gfp/+ mice. g, Scf-GFP was expressed by rare non-haematopoietic stromal cells (n=8). f, Irradiated mice (CD45.1+) were transplanted with 3×10 5 newborn liver cells from Scf gfp/gfp, Scf gfp/+ or Scf +/+ donor (CD45.2+) mice along with 3×10 5 recipient (CD45.1+) bone marrow cells (3-4 experiments with 13-18 mice/genotype). d and e, Newborn liver cellularity and HSC frequency (n=4).
c, Scf transcripts in livers from newborn mice by qRT-PCR (n=3). Thus, HSCs reside in a perivascular niche in which multiple cell types express factors that promote HSC maintenance.Ī and b, Scf gfp/gfp homozygous mice died perinatally and were severely anemic (n=4-20). Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic cells, osteoblasts, nestin-cre- or nestin-creER-expressing cells. Here, using Scf(gfp) knock-in mice, we found that Scf was primarily expressed by perivascular cells throughout the bone marrow. Stem cell factor (SCF also known as KITL) is a key niche component that maintains HSCs. Thus, the cellular sources of these factors are undetermined. However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Several cell types have been proposed to create niches for haematopoietic stem cells (HSCs).
0 kommentar(er)
