title: Nf2/merlin regulates hematopoietic stem cell behavior by altering microenvironmental architecture.
abstract: Stem cell population size is highly regulated across species and tissue types, and alterations are associated with premature tissue failure or cancer. We assessed whether the tumor suppressor and mediator of cell contact inhibition Nf2/merlin plays a role in governing the hematopoietic stem cell pool by stem cell-autonomous or niche-determined processes. Hematopoietic stem cells in Nf2-deficient mice were increased in number and demonstrated a marked shift in location to the circulation. These changes were entirely dependent on changes in the microenvironment, with a marked increase in trabecular bone and marrow vascularity associated with increased VEGF, but without cell-autonomous alterations in stem cell characteristics. Nf2/merlin is critical for maintaining normal structure and function of the hematopoietic stem cell niche. It limits both bone and vascular components, and our model suggests that it thereby constrains stem cell number and position.
authors.affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jonas
authors.initials: J
authors.lastname: Larsson
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ohishi
authors.forename: Brian
authors.initials: B
authors.lastname: Garrison
authors.forename: Marie
authors.initials: M
authors.lastname: Aspling
authors.forename: Viktor
authors.initials: V
authors.lastname: Janzen
authors.forename: Gregor B
authors.initials: GB
authors.lastname: Adams
authors.forename: Marcello
authors.initials: M
authors.lastname: Curto
authors.forename: Andrea I
authors.initials: AI
authors.lastname: McClatchey
authors.forename: Ernestina
authors.initials: E
authors.lastname: Schipani
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
mesh_terms: D000818:Animals; D017209:Apoptosis; D003114:Colony-Forming Units Assay; D003260:Contact Inhibition / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D055153:Stem Cell Niche; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D025581:Neurofibromin 2; D042461:Vascular Endothelial Growth Factor A