Age-related impairment in cell-cell communication in the HSC niche correlates with a decrease in lymphoid differentiation of HSCs. (A) In the young HSC niche, HSCs receive signals from MSCs (blue ligands) and from the blood (red ligands). (B) In the aged HSC niche, HSC-MSC ligand-receptor interactions are impaired. These impairments may be induced by: (i) cell intrinsic changes in MSCs (aged cell morphology), leading to reduced secretion of MSC-derived ligands (blue ligands); or (ii) changes in signaling factors that enter the niche from the blood (red ligands) and/or by retrograde signaling from the aged HSCs (pink ligands), thereby perturbing signaling from MSC-derived ligands to HSCs.