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

Kyung-Rok Yu, Diego A. Espinoza, Chuanfeng Wu, Lauren Truitt, Tae-Hoon Shin, Shirley Chen, Xing Fan, Idalia Yabe, Sandhya Panch, So Gun Hong, Samson Koelle, Rong Lu, Aylin Bonifacino, Allen Krouse, Mark Metzger, Robert E. Donahue and Cynthia E. Dunbar

Key points

  • Genetic barcoding of HSPC in aged rhesus macaques reveals impaired long-term multipotent clonal output with clonal hematopoiesis


Age-associated changes in hematopoietic stem and progenitor cells (HSPC) 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 HSPC in aged versus young macaques following autologous transplantation. Aged macaques showed delayed emergence of output from multipotent clones, with persistence of lineage-biased clones for many months following engraftment. In contrast to murine aging models reporting persistence of myeloid-biased HSPC, aged macaques demonstrated persistent output from both B cell and myeloid-biased clones. Clonal expansions of multipotent, myeloid-biased and B-biased clones occurred in aged macaques, providing a potential model for human clonal hematopoiesis of indeterminate prognosis (CHIP). These results suggest long-term multipotent 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.

  • Submitted August 17, 2017.
  • Accepted December 21, 2017.