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

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.