title: 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 of Ghr signaling in hematopoietic stem cell (HSC) biology remains unexplored. Within the hematopoietic system, Ghr is expressed in a highly HSC-specific manner and is significantly upregulated during aging. Exposure of young and old HSCs to recombinant growth hormone ex vivo led to diminished 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 induces age-dependent HSC effects, these results indicate that Ghr signaling appears largely dispensable for HSC function and aging.
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA; and.
authors.forename: Morag H
authors.initials: MH
authors.lastname: Stewart
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA; and.
authors.forename: Paula
authors.initials: P
authors.lastname: Gutierrez-Martinez
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA; and.
authors.forename: Isabel
authors.initials: I
authors.lastname: Beerman
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA; and.
authors.forename: Brian
authors.initials: B
authors.lastname: Garrison
authors.affiliation: Division of Medicine, Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Gallagher
authors.affiliation: Division of Medicine, Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY.
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA; Department of Stem Cell and Regenerative Medicine, Harvard University, Cambridge, MA; and.
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Rossi
mesh_terms: D000375:Aging; D000818:Animals; D016922:Cellular Senescence; D017353:Gene Deletion; D015870:Gene Expression; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011986:Receptors, Somatotropin; D013006:Growth Hormone