ATP2B1 expression identifies human hematopoietic stem cells across ontogeny with superior repopulation and self-renewal capacity

The human LT-HSC compartment is molecularly and functionally heterogeneous and also varies across ontogeny. Dissecting the molecular basis for this variation is impeded by the absence of immunophenotypic markers to resolve LT-HSC heterogeneity.

Here, we identified ATPase plasma membrane Ca2+transporting 1 (ATP2B1/PMCA1) as a novel cell surface marker that is heterogeneously expressed by CD49f+ LT-HSC across ontogeny. ATP2B1 immunophenotypic expression stratified human CD49f+ LT-HSC from fetal liver (FL), neonatal cord blood (CB) and adult mobilized peripheral blood (mPB) sources into functionally distinct subpopulations in single-cell (sc) clonogenic assays. CD49f+ATP2B1+ LT-HSC exhibited superior long-term repopulation and self-renewal capacities in vivo compared to CD49f+ATP2B1– LT-HSC.