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.


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.


CONCLUSIONS
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.
Bradfute
Steven B
SB
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Graubert
Timothy A
TA
Goodell
Margaret A
MA
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D003062:Codon / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis
D000950:Antigens, Ly; D003062:Codon; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins