[PDF][PDF] SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors

H Oguro, L Ding, SJ Morrison - Cell stem cell, 2013 - cell.com
H Oguro, L Ding, SJ Morrison
Cell stem cell, 2013cell.com
Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are
routinely isolated using various markers but remain heterogeneous. Here we show that four
SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs
from restricted progenitors and subdivide them into a hierarchy of functionally distinct
subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting
potential. CD229 expression largely distinguished lymphoid-biased HSCs from rarely …
Summary
Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) are routinely isolated using various markers but remain heterogeneous. Here we show that four SLAM family markers, CD150, CD48, CD229, and CD244, can distinguish HSCs and MPPs from restricted progenitors and subdivide them into a hierarchy of functionally distinct subpopulations with stepwise changes in cell-cycle status, self-renewal, and reconstituting potential. CD229 expression largely distinguished lymphoid-biased HSCs from rarely dividing myeloid-biased HSCs, enabling prospective enrichment of these HSC subsets. Differences in CD229 and CD244 expression resolved CD150CD48−/lowLineage−/lowSca-1+c-Kit+ cells into a hierarchy of highly purified MPPs that retained erythroid and platelet potential but exhibited progressive changes in mitotic activity and reconstituting potential. Use of these markers, and reconstitution assays, showed that conditional deletion of Scf from endothelial cells and perivascular stromal cells eliminated the vast majority of bone marrow HSCs, including nearly all CD229−/low HSCs, demonstrating that quiescent HSCs are maintained by a perivascular niche.
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