Atlas of Cynomolgus Macaque Hematopoiesis

Self-renewal and differentiation are inherent properties of hematopoietic stem cells that are necessary to support hematopoiesis. However, the underlying mechanisms, especially in human, remain unclear. Here, using the cynomolgus macaque as a surrogate model, we develop a new gating strategy to isolate with high purity transplantable cynomolgus HSCs and generated a single-cell transcriptomic map of cynomolgus HSCs and progenitor cells, that covers the gestational period not analyzed in human. We show that hematopoietic cells from the late-1st to early-3rd trimester fetal liver and late-2nd trimester and thereafter bone marrow has repopulating potential, closely mimicking humans. Unexpectedly however, we found unlike in human, cynomolgus HSCs express CD38 but not CD33, indicating that these cellular counterparts are molecularly distinct. Our transcriptomic analysis reveals the presence of a direct differentiation pathway from HSCs to megakaryocyte lineages, lineage-primed multipotent progenitors and also identified putative HSC surface markers. Taken together, our comprehensive dataset highlights not only the utility of cynomolgus monkeys as model systems to study hematopoiesis but also their potential for translational applications. To obtain transcriptomic landscape of cynomolgus macaque hamatopoiesis across developmental stages, we analyzed CD34 positive hematopoietic cells of early 2nd FL, late 2nd FL, early 3rd FL, late 2nd FBM, early 3rd FBM and ABM using 10X Genomics 5’ chemistry based single-cell RNA-sequencing.