Project description: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.
Project description:Infinium 450K is a hybridization array designed for the human genome, but the relative conservation between the macaque and human genomes makes its use in macaques feasible. We used the Infinium450K array to assay twelve Cynomolgus macaque muscle biopsies and compared it to Reduced Representation Bisulphite Sequencing (RRBS) data generated on the same samples.
Project description:Infinium 450K is a hybridization array designed for the human genome, but the relative conservation between the macaque and human genomes makes its use in macaques feasible. We used the Infinium450K array to assay twelve Cynomolgus macaque muscle biopsies and compared it to Reduced Representation Bisulphite Sequencing (RRBS) data generated on the same samples.
Project description:Infinium 450K is a hybridization array designed for the human genome, but the relative conservation between the macaque and human genomes makes its use in macaques feasible. We used the Infinium450K array to assay twelve Cynomolgus macaque muscle biopsies and compared it to Reduced Representation Bisulphite Sequencing (RRBS) data generated on the same samples. Muscle biopsies were performed on eleven adult male cynomologus macaques
Project description:Infinium 450K is a hybridization array designed for the human genome, but the relative conservation between the macaque and human genomes makes its use in macaques feasible. We used the Infinium450K array to assay twelve Cynomolgus macaque muscle biopsies and compared it to Reduced Representation Bisulphite Sequencing (RRBS) data generated on the same samples. Muscle biopsies were performed on eleven adult male cynomologus macaques