Lymphoid-Biased Hematopoietic Stem Cells Are Maintained with Age and Efficiently Generate Lymphoid Progeny

Current models propose that reductions in the number of lymphoid-biased hematopoietic stem cells (Ly-HSCs) underlie age-related declines in lymphopoiesis. We show that Ly-HSCs do not decline in number with age. Old Ly-HSCs exhibit changes in gene expression and a myeloid-biased genetic profile, but we demonstrate that they retain normal lymphoid potential when removed from the old in vivo environment. Additional studies showing that interleukin-1 inhibits Ly-HSC lymphoid potential provide support for the hypothesis that increased production of inflammatory cytokines during aging underlies declines in lymphocyte production. These results indicate that current models proposing that lymphopoiesis declines with age due to loss of Ly-HSCs require revision and provide an additional perspective on why lymphocyte development in the elderly is attenuated. [Display omitted] •Ly-HSCs do not decline in number with age•Transcriptome changes in old Ly-HSCs result in the acquisition of a myeloid signature•Ly-HSCs efficiently generate lymphocytes when removed from the old environment•IL-1 blocks lymphoid potential from Ly-HSCs and My-HSCs Dorshkind and colleagues challenge the existing model proposing that the age-related decline in lymphocyte development results from the loss of Ly-HSCs. They show that Ly-HSC number does not decline with age and that, despite transcriptome changes and acquisition of a myeloid-biased pattern of gene expression, Ly-HSCs retain normal lymphoid developmental potential when removed from the old marrow environment.