title: Quantitative stability of hematopoietic stem and progenitor cell clonal output in rhesus macaques receiving transplants.
abstract: Autologous transplantation of hematopoietic stem and progenitor cells lentivirally labeled with unique oligonucleotide barcodes flanked by sequencing primer targets enables quantitative assessment of the self-renewal and differentiation patterns of these cells in a myeloablative rhesus macaque model. Compared with other approaches to clonal tracking, this approach is highly quantitative and reproducible. We documented stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells, and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in 4 macaques observed for up to 49 months posttransplantation. A broad range of clonal behaviors characterized by contribution level and biases toward certain cell types were extremely stable over time. Correlations between granulocyte and monocyte clonalities were greatest, followed by correlations between these cell types and B cells. We also detected quantitative expansion of T cell-biased clones consistent with an adaptive immune response. In contrast to recent data from a nonquantitative murine model, there was little evidence for clonal succession after initial hematopoietic reconstitution. These findings have important implications for human hematopoiesis, given the similarities between macaque and human physiologies.
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.|Department of Statistics, University of Washington, Seattle, WA.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Samson J
authors.initials: SJ
authors.lastname: Koelle
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Diego A
authors.identifier: 0000-0002-9627-6508
authors.initials: DA
authors.lastname: Espinoza
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Chuanfeng
authors.identifier: 0000-0001-5509-5754
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Statistics, University of Washington, Seattle, WA.
authors.forename: Jason
authors.identifier: 0000-0001-5472-3720
authors.initials: J
authors.lastname: Xu
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA.
authors.forename: Rong
authors.identifier: 0000-0002-5151-9246
authors.initials: R
authors.lastname: Lu
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Brian
authors.identifier: 0000-0001-7321-776X
authors.initials: B
authors.lastname: Li
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Robert E
authors.identifier: 0000-0003-4021-3986
authors.initials: RE
authors.lastname: Donahue
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Cynthia E
authors.identifier: 0000-0002-7645-838X
authors.initials: CE
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D000066673:Cell Self Renewal; D002999:Clone Cells / Q000166:cytology; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008253:Macaca mulatta