Cell stem cell, 2013-07, Vol.13 (1), p.102-116
2013
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- Autor(en) / Beteiligte
- Titel
- SLAM Family Markers Resolve Functionally Distinct Subpopulations of Hematopoietic Stem Cells and Multipotent Progenitors
- Ist Teil von
- Cell stem cell, 2013-07, Vol.13 (1), p.102-116
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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−/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. •LSK cells can be subdivided into a hierarchy of 7 populations using 4 SLAM markers•CD229 expression distinguishes functionally distinct subsets of HSCs and MPPs•CD229− HSCs are mainly myeloid biased and more quiescent than CD229+ HSCs•Most HSCs, including CD229− quiescent HSCs, are maintained by a perivascular niche Expansion of the range of SLAM family marker combinations allows prospective enrichment of distinct subpopulations of hematopoietic stem cells and multipotent progenitors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1934-5909eISSN: 1875-9777DOI: 10.1016/j.stem.2013.05.014Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3736853
- Format
- –
- Schlagworte
- Animals, Antigens, CD - metabolism, Biomarkers - metabolism, Blotting, Western, Bone Marrow Cells - cytology, Bone Marrow Cells - metabolism, CD48 Antigen, Cell Cycle, Cell Differentiation, Cell Proliferation, Cell Separation, Chemokine CXCL12 - metabolism, Colony-Forming Units Assay, Endothelial Cells - cytology, Endothelial Cells - metabolism, Female, Flow Cytometry, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - metabolism, Lymphoid Progenitor Cells - cytology, Lymphoid Progenitor Cells - metabolism, Male, Mice, Mice, Inbred C57BL, Multipotent Stem Cells - cytology, Multipotent Stem Cells - metabolism, Myeloid Progenitor Cells - cytology, Myeloid Progenitor Cells - metabolism, Receptors, Cell Surface - metabolism, Receptors, Immunologic - metabolism, Signaling Lymphocytic Activation Molecule Family, Signaling Lymphocytic Activation Molecule Family Member 1, Stromal Cells - cytology, Stromal Cells - metabolism