Ding et al Critical Analysis
In their 2012 report, Ding and his colleagues demonstrate that hematopoietic stem cells (HSCs) reside in a perivascular niche, where Scf plays an indispensible role in the maintenance of its niche. Although it has been known that Scf and other factors promote HSC maintenance, there has not been enough evidence to definitively state the cellular sources of these factors. Ding and his colleagues are able to indicate for the first time that Scf from both endothelial and perivascular cells are crucial to the maintenance of HSC by generating and examining knock-in Scfgfp and knock out Scffl mice. This discover may lead to a better understanding of the mechanisms by which cells promote stem cell maintenance and expansion.
The first breakthrough of understanding the niche, which blood-forming stem cells reside, was when Ding and his colleagues systematically determined which cells are the sources of Scf through a number of remarkable strategies. Ding and his team first generated Scf/gfp knock in mouse by swapping an scf gene with gfp. Scf gfp/gfp homozygous mice died perinatally and were found unable to regenerate blood cells. Scf gfp/+ mice demonstrated GFP expression primarily by perivascular cells surrounding sinusoids throughout the bone marrow (Fig.1h-m). Through gene expression profiling, ding and his team found that Scf-GFP+ cells form a perivascular niche for the HSCs.
In order to determine whether Scf is necessary and required by adult hematopoietic stem cells, Scf expression was eliminated in each niche cell through the generation of floxed allele of Scf (Scffl). By generating Ubc-creER mice with deleted Scf with Tamoxifen treatment, investigators found that the mice had significantly lower amounts of red blood cells and became anaemic (Fig. 2c). When investigators generated Col2.3-Cre; Scffl- mice to test whether SCF from osteoblasts are required for HSCs, they found that the mice had normal blood counts, and normal bone marrow and spleen cellularity
The first breakthrough of understanding the niche, which blood-forming stem cells reside, was when Ding and his colleagues systematically determined which cells are the sources of Scf through a number of remarkable strategies. Ding and his team first generated Scf/gfp knock in mouse by swapping an scf gene with gfp. Scf gfp/gfp homozygous mice died perinatally and were found unable to regenerate blood cells. Scf gfp/+ mice demonstrated GFP expression primarily by perivascular cells surrounding sinusoids throughout the bone marrow (Fig.1h-m). Through gene expression profiling, ding and his team found that Scf-GFP+ cells form a perivascular niche for the HSCs.
In order to determine whether Scf is necessary and required by adult hematopoietic stem cells, Scf expression was eliminated in each niche cell through the generation of floxed allele of Scf (Scffl). By generating Ubc-creER mice with deleted Scf with Tamoxifen treatment, investigators found that the mice had significantly lower amounts of red blood cells and became anaemic (Fig. 2c). When investigators generated Col2.3-Cre; Scffl- mice to test whether SCF from osteoblasts are required for HSCs, they found that the mice had normal blood counts, and normal bone marrow and spleen cellularity