Format

Send to

Choose Destination
Blood. 2018 Mar 15;131(11):1195-1205. doi: 10.1182/blood-2017-08-802033. Epub 2018 Jan 2.

The impact of aging on primate hematopoiesis as interrogated by clonal tracking.

Author information

1
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
2
Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC.
3
Department of Statistics, University of Washington, Seattle, WA; and.
4
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA.

Abstract

Age-associated changes in hematopoietic stem and progenitor cells (HSPCs) have been carefully documented in mouse models but poorly characterized in primates and humans. To investigate clinically relevant aspects of hematopoietic aging, we compared the clonal output of thousands of genetically barcoded HSPCs in aged vs young macaques after autologous transplantation. Aged macaques showed delayed emergence of output from multipotent (MP) clones, with persistence of lineage-biased clones for many months after engraftment. In contrast to murine aging models reporting persistence of myeloid-biased HSPCs, aged macaques demonstrated persistent output from both B-cell and myeloid-biased clones. Clonal expansions of MP, myeloid-biased, and B-biased clones occurred in aged macaques, providing a potential model for human clonal hematopoiesis of indeterminate prognosis. These results suggest that long-term MP HSPC output is impaired in aged macaques, resulting in differences in the kinetics and lineage reconstitution patterns between young and aged primates in an autologous transplantation setting.

PMID:
29295845
PMCID:
PMC5855019
DOI:
10.1182/blood-2017-08-802033
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center