Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding

Blood. 2013 Jul 25;122(4):523-32. doi: 10.1182/blood-2013-01-481135. Epub 2013 May 29.

Abstract

The number of hematopoietic stem cells (HSCs) that contributes to blood formation and the dynamics of their clonal contribution is a matter of ongoing discussion. Here, we use cellular barcoding combined with multiplex high-throughput sequencing to provide a quantitative and sensitive analysis of clonal behavior of hundreds of young and old HSCs. The majority of transplanted clones steadily contributes to hematopoiesis in the long-term, although clonal output in granulocytes, T cells, and B cells is substantially different. Contributions of individual clones to blood are dynamically changing; most of the clones either expand or decline with time. Finally, we demonstrate that the pool of old HSCs is composed of multiple small clones, whereas the young HSC pool is dominated by fewer, but larger, clones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / blood*
  • Animals
  • Blood Donors*
  • Cell Separation / methods
  • Cell Tracking / methods*
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Clonal Evolution / physiology*
  • Clone Cells / cytology
  • Clone Cells / physiology
  • DNA Barcoding, Taxonomic / methods
  • DNA Barcoding, Taxonomic / statistics & numerical data
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Molecular Typing / methods