Journal
BLOOD
Volume 122, Issue 18, Pages 3129-3137Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-06-508432
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Funding
- Canadian Institutes of Health Research (CIHR)
- Canadian Stem Cell Network
- Terry Fox Foundation [TFF-122869]
- Health Canada
- Public Health Agency of Canada
- Croucher Foundation Fellowship from Hong Kong
- CIHR Vanier Canada Studentships
- Kay Kendall Leukemia Fund Intermediate Fellowship from the United Kingdom
- CIHR Transplantation Training Program Scholarship
- CIHR Doctoral Award
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Human cord blood (CB) offers an attractive source of cells for clinical transplants because of its rich content of cells with sustained repopulating ability in spite of an apparent deficiency of cells with rapid reconstituting ability. Nevertheless, the clonal dynamics of nonlimiting CB transplants remain poorly understood. To begin to address this question, we exposed CD34(+) CB cells to a library of barcoded lentiviruses and used massively parallel sequencing to quantify the clonal distributions of lymphoid and myeloid cells subsequently detected in sequential marrow aspirates obtained from 2 primary NOD/SCID-IL2R gamma(-/-) mice, each transplanted with similar to 10(5) of these cells, and for another 6 months in 2 secondary recipients. Of the 196 clones identified, 68 were detected at 4 weeks posttransplant and were often lymphomyeloid. The rest were detected later, after variable periods up to 13 months posttransplant, but with generally increasing stability throughout time, and they included clones in which different lineages were detected. However, definitive evidence of individual cells capable of generating T-, B-, and myeloid cells, for over a year, and self-renewal of this potential was also obtained. These findings highlight the caveats and utility of this model to analyze human hematopoietic stem cell control in vivo.
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