Roles of Sca-1 in hematopoietic stem/progenitor cell function

Objective. This study was focused on studying the role of Sca-1 (Ly-6 A/E) in hematopoietic stem/progenitor cell self-renewal, activation, and lineage fate. Materials and Methods. Sca-1(-/-) bone marrow cells were transplanted into wild-type recipient mice and assessed for self-renewal activity and lineage choice. In addition, Sca-1(-/-) mice were injected with 5-FU and Lin(-) cells were analyzed. Sca-1 was also overexpressed in mouse and human stem/progenitor cells to assess the effect of Sca-1 overexpression on stem/progenitor differentiation and proliferation. Results. Self-renewal of Sca-1(-/-) HSC appeared to be normal, but lineage skewing was observed in B cells, NK cells, and granulocytes/macrophages derived from Sca-1-/- HSC. There was also a decrease in c-kit expression on activated Sca-1(-/-) progenitor cells. Overexpression of mouse Sca-1 decreased the in vitro myeloid activity of both mouse and human progenitors. Conclusion. These data indicate that Sca-1 plays a role in hematopoietic progenitor/stem cell lineage fate and c-kit expression. In addition, mouse Sca-1 overexpression affects human as well as mouse stem/progenitor cell activity, suggesting the possibility of a functional human Sca-1 homologue. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.