A single-cell transcriptomic atlas of rhesus macaque hematopoiesis reveals age-related myeloid bias and differentiation changes

While murine models have provided critical insights into hematopoietic stem cell (HSC) aging, the evolutionary distance to humans limits their translational applicability. Non-human primates, such as rhesus macaques, offer a highly relevant model, yet a comprehensive single-cell transcriptomic map of their aging hematopoietic system has been lacking.

Here, we present a high-resolution single-cell RNA sequencing atlas of rhesus macaque hematopoiesis, profiling whole bone marrow, peripheral blood, and CD34-enriched progenitor cells from young and late-middle-aged cohorts. Our analysis delineates the transcriptional landscape of macaque hematopoiesis and identifies robust surface markers for prospective isolation of progenitor subpopulations. We uncover distinct, lineage-specific aging signatures, with the most profound transcriptional alterations occurring in multipotent progenitors and classical monocytes.