Parsing the niche code: the molecular mechanisms governing hematopoietic stem cell adhesion and differentiation

Evidence that Growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells

“…2 It is possible that loss of Gfi1b causes a delocalization of HSCs away from the hypoxic endosteal niche to a more oxygen rich environment, which drives them into the cell cycle and causes a significant expansion in bone marrow and blood. Our finding that VCAM-1, integrin ␣4, and CXCR4, which have been described to play an important role in keeping HSCs in a dormant state in their endosteal niche, 1,6,[39][40][41][42] are all down-regulated in Gfi1b ko/ko HSCs, points to this as a possible explanation for the activation of Gfi1b-deficient HSCs. Dysregulation of surface proteins regulating retention of HSCs in the endosteal niche could lead to the release of Gfi1b ko/ko HSCs from the hypoxic endosteal niche.…”

“…We found that genes encoding cell adhesion molecules and integrins were profoundly deregulated in Gfi1b ko/ko HSCs (Figure 7C-D). Notably, such proteins as vascular cell adhesion protein 1 (VCAM-1), CXCR4, and integrin ␣4 that are important to retain HSCs in their endosteal niche 1,6,[39][40][41][42] were expressed at significantly lower levels on Gfi1b ko/ko HSCs compared with wt HSCs ( Figure 7D-E and Table 5). On the other hand, adhesion molecules such as integrin ␤1 and ␤3 that mediate endothelial adhesion 43,44 were significantly up-regulated at mRNA and protein level ( Figure 7D-E and Table 5), suggesting that loss of Gfi1b directly or indirectly affects expression of cell surface molecules that have a role in niche organization.…”

CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and function

“…15 HSC have been shown to localize nearby stromal cells expressing high levels of SDF-1. 16 But still, HSC lacking CXCR-4 are able to home and engraft back into the BM, although with a lower efficiency.…”

CD31 expression on peripheral blood stem cells predicts both early neutrophil and platelet engraftments

“…It is a prerequisite process for proper HSC function upon transplantation and is defined as the ability to travel through the blood stream and find specialized bone marrow niches. It is likely that both the homing and engraftment processes are accomplished through a combination of (a) passive travel of HSCs through the blood, (b) relocation from the vasculature to the bone marrow by active extravasation, and (c) engraftment in bone marrow niches by molecular interactions with numerous niche components [8][9][10][11].…”