Highly-multiplexed mass cytometry screen of human bone marrow hematopoietic stem and progenitor cells

<p>In contrast to the rich single-cell transcriptomic and epigenetic data, the corresponding protein level information of human hematopoietic stem and progenitor cell (HSPC) populations is still missing. We used a highly-multiplexed single-cell screen to quantify the protein expression of 353 surface molecules and 79 functional intracellular molecules (TFs, chromatin regulators, and metabolic enzymes) with mass cytometry. In doing this, we created a core panel with probes against functional protein molecules associated with specific lineage potentials to better illuminate the differentiation potentials of the progenitors. In total, we analyzed 556,226 CD34+ bone marrow HSPCs across three individuals. Our analysis identified ten distinct clusters among HSPCs by unsupervised method and defined their unique proteomic composition. We compare our data-driven populations to the canonical HSPC cell types identified by cell surface proteins and observe discrepancies, especially in the lympho-myeloid axis. Overall, we supply a quantified summary of the proteomes of human HSPCs and create a framework to redefine progenitor populations with unique functional states along hematopoiesis. </p>