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Cell Stem Cell. 2014 Apr 3;14(4):486-499. doi: 10.1016/j.stem.2014.01.020.

Clonal tracking of rhesus macaque hematopoiesis highlights a distinct lineage origin for natural killer cells.

Author information

1
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
2
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
3
DNA Sequencing and Genomics Core; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
4
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
5
Office of Biostatistics Research, National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
6
UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
#
Contributed equally

Abstract

Analysis of hematopoietic stem cell function in nonhuman primates provides insights that are relevant for human biology and therapeutic strategies. In this study, we applied quantitative genetic barcoding to track the clonal output of transplanted autologous rhesus macaque hematopoietic stem and progenitor cells over a time period of up to 9.5 months. We found that unilineage short-term progenitors reconstituted myeloid and lymphoid lineages at 1 month but were supplanted over time by multilineage clones, initially myeloid restricted, then myeloid-B clones, and then stable myeloid-B-T multilineage, long-term repopulating clones. Surprisingly, reconstitution of the natural killer (NK) cell lineage, and particularly the major CD16(+)/CD56(-) peripheral blood NK compartment, showed limited clonal overlap with T, B, or myeloid lineages, and therefore appears to be ontologically distinct. Thus, in addition to providing insights into clonal behavior over time, our analysis suggests an unexpected paradigm for the relationship between NK cells and other hematopoietic lineages in primates.

PMID:
24702997
PMCID:
PMC3979461
DOI:
10.1016/j.stem.2014.01.020
[Indexed for MEDLINE]
Free PMC Article

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