title: Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche.
abstract: Haematopoietic stem-progenitor cells (HSPCs) reside in the bone marrow niche, where interactions with osteoblasts provide essential cues for their proliferation and survival. Here, we use live-cell imaging to characterize both the site of contact between osteoblasts and haematopoietic progenitor cells (HPCs) and events at this site that result in downstream signalling responses important for niche maintenance. HPCs made prolonged contact with the osteoblast surface through a specialized membrane domain enriched in prominin 1, CD63 and rhodamine PE. At the contact site, portions of the specialized domain containing these molecules were taken up by the osteoblast and internalized into SARA-positive signalling endosomes. This caused osteoblasts to downregulate Smad signalling and increase production of stromal-derived factor-1 (SDF-1), a chemokine responsible for HSPC homing to bone marrow. These findings identify a mechanism involving intercellular transfer to signalling endosomes for targeted regulation of signalling and remodelling events within an ex vivo osteoblastic niche.
authors.affiliation: Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Gillette
authors.forename: Andre
authors.initials: A
authors.lastname: Larochelle
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lippincott-Schwartz
mesh_terms: D001853:Bone Marrow / Q000378:metabolism*; D002450:Cell Communication; D002451:Cell Compartmentation; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D021962:Membrane Microdomains / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D051785:Smad Proteins