Open AccessDifferential Expression of α2 Integrin Separates Long‐Term and Short‐Term Reconstituting Lin −/lo Thy1.1 lo c‐kit + Sca‐1 + Hematopoietic Stem Cells
Author(s) -
Wagers Amy J.,
Weissman Irving L.
Publication year - 2006
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2005-0396
Subject(s) - biology , stem cell , haematopoiesis , cell sorting , bone marrow , population , progenitor cell , lineage markers , microbiology and biotechnology , stem cell marker , side population , immunology , cancer stem cell , flow cytometry , demography , sociology
Self‐renewing, multipotent hematopoietic stem cells are highly enriched within the Lin − Thy1.1 lo c‐kit + Sca‐1 + subset of mouse bone marrow. However, heterogeneous expression within this population of certain cell surface markers raises the possibility that it may be further fractionated phenotypically and perhaps functionally. We previously identified α2‐integrin (CD49b) as a surface marker with heterogeneous expression on Lin − /lo Thy1.1 lo c‐kit + Sca‐1 + stem cells. To determine whether differences in α2 expression were indicative of differences in stem cell function, we purified α2 − and α2 hi stem cells by fluorescence‐activated cell sorting and analyzed their function in long‐ and short‐term hematopoietic reconstitution assays. Both α2 − and α2 hi cells could give rise to mature lymphoid and myeloid cells after transplantation into lethally irradiated congenic recipients. However, α2 hi cells supported hematopoiesis for only a short time (<4 weeks), whereas α2 − cells reproducibly yielded robust, long‐term (>20 weeks) reconstitution, suggesting that α2 − cells represent a more primitive population than do α2 hi cells. Consistent with this idea, α2 − Lin − /lo Thy1.1 lo c‐kit + Sca‐1 + cells exhibited an approximately sixfold decreased frequency of spleen colony‐forming units (day 12) versus α2 hi cells. Furthermore, bone marrow cells isolated from animals transplanted >20 weeks previously with 20 α2 − Lin − /lo Thy1.1 lo c‐kit + Sca‐1 + cells included both α2 − and α2 hi stem cells of donor origin, indicating that α2 hi cells are likely lineal descendents of α2 − cells. Interestingly, α2 integrin expression is significantly reduced on lineage‐restricted oligopotent progenitors in the marrow, suggesting that high level expression of α2 selectively marks a subset of primitive hematopoietic cells which retains multilineage reconstitution potential but exhibits reduced self‐renewal capacity.