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

Abstract:

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.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Bradfute SB,Graubert TA,Goodell MA

doi

10.1016/j.exphem.2005.04.001

keywords:

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

836-43

issue

7

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(05)00175-X

journal_volume

33

pub_type

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