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Blood. 2017 Mar 16;129(11):1448-1457. doi: 10.1182/blood-2016-07-728691. Epub 2017 Jan 13.

Quantitative stability of hematopoietic stem and progenitor cell clonal output in rhesus macaques receiving transplants.

Author information

1
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
2
Department of Statistics, University of Washington, Seattle, WA.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
4
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA.

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.

PMID:
28087539
PMCID:
PMC5356453
DOI:
10.1182/blood-2016-07-728691
[Indexed for MEDLINE]
Free PMC Article

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