title: Upregulation of CD11A on hematopoietic stem cells denotes the loss of long-term reconstitution potential.
abstract: Small numbers of hematopoietic stem cells (HSCs) generate large numbers of mature effector cells through the successive amplification of transiently proliferating progenitor cells. HSCs and their downstream progenitors have been extensively characterized based on their cell-surface phenotype and functional activities during transplantation assays. These cells dynamically lose and acquire specific sets of surface markers during differentiation, leading to the identification of markers that allow for more refined separation of HSCs from early hematopoietic progenitors. Here, we describe a marker, CD11A, which allows for the enhanced purification of mouse HSCs. We show through in vivo transplantations that upregulation of CD11A on HSCs denotes the loss of their long-term reconstitution potential. Surprisingly, nearly half of phenotypic HSCs (defined as Lin-KIT(+)SCA-1(+)CD150(+)CD34-) are CD11A(+) and lack long-term self-renewal potential. We propose that CD11A(+)Lin-KIT(+)SCA-1(+)CD150(+)CD34- cells are multipotent progenitors and CD11A-Lin-KIT(+)SCA-1(+)CD150(+)CD34- cells are true HSCs.
authors.affiliation: Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: jfathman@gnf.org.
authors.forename: John W
authors.initials: JW
authors.lastname: Fathman
authors.affiliation: Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Nathaniel B
authors.initials: NB
authors.lastname: Fernhoff
authors.affiliation: Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Seita
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Chao
authors.affiliation: Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Scarfone
authors.affiliation: Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA. Electronic address: minlay@uci.edu.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Inlay
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000950:Antigens, Ly; D040881:CD11a Antigen; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019009:Proto-Oncogene Proteins c-kit