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.
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Acknowledgements
We are grateful to Victoria Cogger (University of Sydney, ANZAC Research Institute, Australia) for assistance with scanning electron microscopy. We would also like to thank Denis Corbeil (University of Dresden, Germany) for providing the prominin 1–GFP construct, and Suliana Manley and George Patterson (NIH) for critical reading of the manuscript. This project was supported by the Intramural Research Program of the US National Institute of Child Health and Human Development, National Institutes of Health.
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J.G. was responsible for designing and completing the experimental work, analysing the data and writing the manuscript; A.L and C.D. isolated and provided primary HPCs and contributed to data and manuscript discussions; J.L-S. supervised the project and wrote the manuscript.
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Gillette, J., Larochelle, A., Dunbar, C. et al. Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche. Nat Cell Biol 11, 303–311 (2009). https://doi.org/10.1038/ncb1838
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DOI: https://doi.org/10.1038/ncb1838
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