title: SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity.
abstract: Recent advances have increased the purity of hematopoietic stem cells (HSCs) isolated from young mouse bone marrow. However, little attention has been paid to the purity of HSCs from other contexts. Although Thy-1 low Sca-1+ Lineage- c-kit+ cells from young bone marrow are highly enriched for HSCs (1 in 5 cells gives long-term multilineage reconstitution after transplantation into irradiated mice), the same population from old, reconstituted, or cytokine-mobilized mice engrafts much less efficiently (1 in 78 to 1 in 185 cells gives long-term multilineage reconstitution). To test whether we could increase the purity of HSCs isolated from these contexts, we examined the SLAM family markers CD150 and CD48. All detectable HSCs from old, reconstituted, and cyclophosphamide/G-CSF-mobilized mice were CD150+ CD48-, just as in normal young bone marrow. Thy-1 low Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice included mainly CD48+ and/or CD150- cells that lacked reconstituting ability. CD150+ CD48- Sca-1+ Lineage- c-kit+ cells from old, reconstituted, or mobilized mice were much more highly enriched for HSCs, with 1 in 3 to 1 in 7 cells giving long-term multilineage reconstitution. SLAM family receptor expression is conserved among HSCs from diverse contexts, and HSCs from old, reconstituted, and mobilized mice engraft relatively efficiently after transplantation when contaminating cells are eliminated.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, Ann Arbor, MI, USA.
authors.forename: Omer H
authors.initials: OH
authors.lastname: Yilmaz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kiel
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000950:Antigens, Ly; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000071178:CD48 Antigen; D002469:Cell Separation; D003520:Cyclophosphamide / Q000008:administration & dosage; D006023:Glycoproteins / Q000378:metabolism*; D006085:Graft Survival / Q000528:radiation effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D018800:Thy-1 Antigens; D014916:Whole-Body Irradiation
chemical_list: D015703:Antigens, CD; D000950:Antigens, Ly; D018906:Antineoplastic Agents, Alkylating; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D006023:Glycoproteins; D007136:Immunoglobulins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D003520:Cyclophosphamide; D019009:Proto-Oncogene Proteins c-kit