Angiopoietin-Like 3 Affects Homing Ability of Hematopoietic Stem Cells.

Abstract 2632

Angiopoietin-like proteins (Angptls) are a seven-member family of secreted glycoproteins that share sequence homology with angiopoietins. It is known that several members of the Angptl family including Angptl3 support ex vivo expansion of hematopoietic stem cells (HSCs). However, the physiological role of Angptls in the hematopoietic system is not well known. Here we show that Angptl3 is expressed by both bone marrow stromal cells and HSCs. To study the intrinsic effect of Angptl3 in mouse HSCs, we isolated the same number of HSCs from wild-type and Angptl3-null mice and performed reconstitution analysis. Adult bone marrow Angptl3-null HSCs showed decreased repopulation compared to wild-type HSCs, suggesting that Angptl3 has cell-autonomous effect on HSC activity. By contrast, HSCs isolated from liver of the null mice had enhanced HSC repopulation activity than their wild-type counterparts. To study whether this effect is caused by difference in homing, we injected CFSE labeled wild-type HSCs and Angptl3 null HSCs into lethally irradiated mice, and checked the homing to bone marrow, spleen, and liver. While homing of these two types of cells to bone marrow or spleen was not significantly different, Angptl3 null HSCs homed better to the liver than the wild-type HSCs. Our result suggests that Angptl3 is important for the retention of HSCs in the bone marrow, and the absence of Angptl3 leads HSCs to move to extramedullary organs such as liver.