Letter abstract
Nature Cell Biology 11, 303 - 311 (2009)
Published online: 8 February 2009 | doi:10.1038/ncb1838
Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche
Jennifer M. Gillette1, Andre Larochelle2, Cynthia E. Dunbar2 & Jennifer Lippincott-Schwartz1
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.
- Cell Biology and Metabolism Program, National Institute of Child Health and Human Development and National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
- Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Correspondence to: Jennifer Lippincott-Schwartz1 e-mail: lippincj@mail.nih.gov
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