Clonal tracking of rhesus macaque hematopoiesis highlights a distinct lineage origin for natural killer cells.
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.
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Chuanfeng
C
Wu
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Brian
B
Li
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Rong
R
Lu
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Samson J
SJ
Koelle
DNA Sequencing and Genomics Core; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Yanqin
Y
Yang
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Alexander
A
Jares
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Alan E
AE
Krouse
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Mark
M
Metzger
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Frank
F
Liang
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
Karin
K
Loré
Office of Biostatistics Research, National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Colin O
CO
Wu
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Robert E
RE
Donahue
UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Irvin S Y
ISY
Chen
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Irving
I
Weissman
Hematology Branch; National Heart, Lung and Blood Institute; National Institutes of Health, Bethesda, MD 20892, USA.
Cynthia E
CE
Dunbar
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D058948:Cell Tracking; D002478:Cells, Cultured; D005822:Genetic Vectors; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008253:Macaca mulatta; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism
D018952:Antigens, CD34