Growth hormone receptor signaling is dispensable for HSC function and aging

Abstract

Growth hormone receptor (Ghr) signaling is important in a wide variety of cellular processes including aging; however, the role ofGhr signaling in hematopoietic stem cell (HSC) biologyremains unexplored. Within the hematopoietic system, Ghrisexpressedin a highly HSC-specific manner and is significantly upregulated during aging. Exposure of youngandold HSCstorecombinantgrowthhormoneexvivo ledtodiminished short-term reconstitution and restored B-cell output from old HSCs. Hematopoietic-specific genetic deletion of Ghr neither impacted steady-state hematopoiesis nor serial transplantation potential. Repeat challenge with 5-fluorouracil showed that Ghr was dispensable for HSC activation and homeostatic recovery in vivo and, after challenge, Ghr-deficient HSCs functioned normally through serial transplantation. Although exogenous Gh inducesage-dependent HSC effects, theseresults indicate that Ghr signaling appears largely dispensable for HSC function and aging.