Aged hematopoietic stem cells (HSCs) show increased expression of myeloid-associated genes at the expense of the expression of lymphoid genes and diminished engraftment after transplantation. In Nature Communications, Grover et al. use single-cell transcriptomics to compare individual HSCs from young and aged mice. Young HSCs have increased expression of genes encoding cell-cycle regulators, while old HSCs show increased expression of genes encoding regulators of the immediate-early response to growth factors and megakaryocyte-platelet lineage programming. Aged HSC populations have an increased frequency of Vwf+ platelet-primed HSCs and an increase in the expression frequency of platelet-specific genes in all HSCs, which corresponds to a greater bias for platelet generation and less lymphoid potential than that of young HSCs. Deletion of FOG-1, which along with GATA-1 is required for platelet-lineage differentiation, restores the lymphoid-reconstitution potential of aged HSCs.

Nat. Commun. (24 March 2016) doi:10.1038/ncomms11075