Postnatal conservation of human blood- and marrow-specific CD34+ hematopoietic phenotypes

Abstract

Previous studies of aging have revealed intrinsically determined alterations in the properties of the hematopoietic stem cell (HSC) and progenitor compartments in mice, with variable evidence of an extension of these findings to humans. To examine more closely the surface phenotypes within the CD34⁺ compartment of human blood and bone marrow from birth to old age, we undertook a 13-parameter phenotypic profile analysis of samples from healthy human donors aged 0-76 years. The results indicate a conserved stability of canonically defined phenotype frequencies within the CD34⁺ compartment across this age spectrum, in contrast to previously reported losses of historically defined progenitor phenotypes associated with lymphoid-restricted outputs with advancing age. Interestingly, multidimensionality reduction of the data also produced an unexpected age-independent landscape that, nevertheless, revealed conserved phenotypic differences between cells isolated from blood or bone marrow samples. These source-specific differences were most notable in the HSC-enriched CD34⁺CD38^-CD45RA^-CD90⁺CD49f⁺ fraction, where they were driven largely by differences in cell surface expression of CD34, CD45, CD90, and CD38. Coordinated changes in the expression of several surface markers were also observed during downstream transitions within the CD34⁺ compartment, suggesting potential new strategies for isolating cell types with more narrowly defined functional properties. Overall, these findings indicate a general conservation during human aging of the phenotypic changes that segregate the major historically defined stages of differentiation within the human CD34⁺ compartment and underscore the selection processes that govern those that enter the circulation or alter their phenotypes therein.