title: Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding.
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.
authors.affiliation: Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Verovskaya
authors.forename: Mathilde J C
authors.initials: MJ
authors.lastname: Broekhuis
authors.forename: Erik
authors.initials: E
authors.lastname: Zwart
authors.forename: Martha
authors.initials: M
authors.lastname: Ritsema
authors.forename: Ronald
authors.initials: R
authors.lastname: van Os
authors.forename: Gerald
authors.initials: G
authors.lastname: de Haan
authors.forename: Leonid V
authors.initials: LV
authors.lastname: Bystrykh
mesh_terms: D000367:Age Factors; D000375:Aging / Q000097:blood*; D000818:Animals; D001782:Blood Donors; D002469:Cell Separation / Q000379:methods; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D060965:Clonal Evolution / Q000502:physiology*; D002999:Clone Cells / Q000166:cytology / Q000502:physiology; D058893:DNA Barcoding, Taxonomic / Q000379:methods / Q000706:statistics & numerical data; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D058889:Molecular Typing / Q000379:methods