The combination of CD49b and CD229 reveals a subset of multipotent progenitors with short-term activity within the hematopoietic stem cell compartment

Abstract

Hematopoiesis is maintained by hematopoietic stem cells (HSCs) that replenish all blood lineages throughout life. It is well-established that the HSC pool is functionally heterogeneous consisting of cells differing in longevity, self-renewal ability, cell proliferation, and lineage differentiation. Although HSCs can be identified through the Lineage-Sca-1+c-Kit+CD48-CD34- CD150+ immunophenotype, the cell surface marker combination does not permit absolute purification of functional HSCs with long-term reconstituting ability. Therefore, prospective isolation of long-term HSCs is crucial for mechanistic understanding of the biological functions of HSCs and for resolving functional heterogeneity within the HSC population. Here, we show that the combination of CD229 and CD49b cell surface markers within the phenotypic HSC compartment identifies a subset of multipotent progenitor cells with high proliferative activity and short-term reconstituting ability. Thus, the addition of CD229 and CD49b to conventional HSC markers permits prospective isolation of functional HSCs by distinguishing MPPs in the HSC compartment. SIGNIFICANCE STATEMENTBlood cells are generated by rare stem cells, which based on their defining features of self-renewal and multipotent abilities, are used in transplantation as curative treatment for blood diseases. Despite their clinical importance, mechanisms of stem cell properties are elusive given the inability to isolate pure blood stem cells for prospective analyses. In this study, we demonstrate that stem cells can be isolated by excluding multipotent progenitors, marked by CD229 and CD49b, from the stem cell compartment. Our study has important implications for the analysis of mechanisms regulating stem cell function and is relevant for clinical applications of stem cells.