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Stem Cell Reports. 2014 Nov 11;3(5):707-15. doi: 10.1016/j.stemcr.2014.09.007. Epub 2014 Oct 16.

Upregulation of CD11A on hematopoietic stem cells denotes the loss of long-term reconstitution potential.

Author information

  • 1Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: jfathman@gnf.org.
  • 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
  • 3Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
  • 4Stanford 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.
  • 5Stanford 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.

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.

PMID:
25418718
PMCID:
PMC4235136
DOI:
10.1016/j.stemcr.2014.09.007
[PubMed - indexed for MEDLINE]
Free PMC Article
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