TY - JOUR
T1 - SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors
AU - Oguro, Hideyuki
AU - Ding, Lei
AU - Morrison, Sean J.
N1 - Funding Information:
This work was supported by the National Heart, Lung and Blood Institute (HL097760), the Howard Hughes Medical Institute (HHMI), and the Cancer Prevention and Research Institute of Texas. L.D. was supported by the Helen Hay Whitney Foundation and by HHMI. H.O. was supported by postdoctoral fellowships from the Japanese Society for the Promotion of Science and from the Uehara Memorial Foundation. H.O. performed most experiments. H.O and L.D. performed experiments in Figures 7C–7E and S7A–S7D. H.O. and S.J.M. designed and interpreted all experiments and wrote the manuscript. The University of Michigan has patented the use of SLAM family markers for the isolation of hematopoietic stem cells.
PY - 2013/7/3
Y1 - 2013/7/3
N2 - 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 CD150-CD48-/low Lineage-/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. 2013
AB - 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 CD150-CD48-/low Lineage-/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. 2013
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U2 - 10.1016/j.stem.2013.05.014
DO - 10.1016/j.stem.2013.05.014
M3 - Article
C2 - 23827712
AN - SCOPUS:84889568419
SN - 1934-5909
VL - 13
SP - 102
EP - 116
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -