SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells.
To improve our ability to identify hematopoietic stem cells (HSCs) and their localization in vivo, we compared the gene expression profiles of highly purified HSCs and non-self-renewing multipotent hematopoietic progenitors (MPPs). Cell surface receptors of the SLAM family, including CD150, CD244, and CD48, were differentially expressed among functionally distinct progenitors. HSCs were highly purified as CD150(+)CD244(-)CD48(-) cells while MPPs were CD244(+)CD150(-)CD48(-) and most restricted progenitors were CD48(+)CD244(+)CD150(-). The primitiveness of hematopoietic progenitors could thus be predicted based on the combination of SLAM family members they expressed. This is the first family of receptors whose combinatorial expression precisely distinguishes stem and progenitor cells. The ability to purify HSCs based on a simple combination of SLAM receptors allowed us to identify HSCs in tissue sections. Many HSCs were associated with sinusoidal endothelium in spleen and bone marrow, though some HSCs were associated with endosteum. HSCs thus occupy multiple niches, including sinusoidal endothelium in diverse tissues.
Howard Hughes Medical Institute and Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Mark J
MJ
Kiel
Omer H
OH
Yilmaz
Toshihide
T
Iwashita
Osman H
OH
Yilmaz
Cox
C
Terhorst
Sean J
SJ
Morrison
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology; D000071178:CD48 Antigen; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006410:Hematopoiesis / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D006023:Glycoproteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1