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Nature 457, 97-101 (1 January 2009) | doi:10.1038/nature07639; Received 28 April 2008; Accepted 14 November 2008; Published online 3 December 2008

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Letter
Nature 457, 97-101 (1 January 2009) | doi:10.1038/nature07639; Received 28 April 2008; Accepted 14 November 2008; Published online 3 December 2008


Detection of functional haematopoietic stem cell niche using real-time imaging
Yucai Xie1,2,5, Tong Yin1,5, Winfried Wiegraebe1, Xi C. He1, Diana Miller3, Danny Stark1, Katherine Perko1, Richard Alexander1, Joel Schwartz1, Justin C. Grindley1, Jungeun Park1, Jeff S. Haug1, Joshua P. Wunderlich1, Hua Li1, Simon Zhang1, Teri Johnson1, Ricardo A. Feldman3 & Linheng Li1,4

Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, Missouri 64110, USA
Department of Cardiology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197, Rui Jin 2 Road, Shanghai 200025, China
Department of Microbiology and Immunology, and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
Department of Pathology and Laboratory Medicine, Kansas University Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA
These authors contributed equally to this work.
Correspondence to: Ricardo A. Feldman3Linheng Li1,4 Correspondence and requests for materials should be addressed to R.A.F. (Email: rfeldman@umaryland.edu) and L.L. (Email: lil@stowers-institute.org).


Top of pageAbstractHaematopoietic stem cell (HSC) niches, although proposed decades ago1, have only recently been identified as separate osteoblastic and vascular microenvironments2, 3, 4, 5, 6. Their interrelationships and interactions with HSCs in vivo remain largely unknown. Here we report the use of a newly developed ex vivo real-time imaging technology and immunoassaying to trace the homing of purified green-fluorescent-protein-expressing (GFP+) HSCs. We found that transplanted HSCs tended to home to the endosteum (an inner bone surface) in irradiated mice, but were randomly distributed and unstable in non-irradiated mice. Moreover, GFP+ HSCs were more frequently detected in the trabecular bone area compared with compact bone area, and this was validated by live imaging bioluminescence driven by the stem-cell-leukaemia (Scl) promoter¨Cenhancer7. HSCs home to bone marrow through the vascular system. We found that the endosteum is well vascularized and that vasculature is frequently localized near N-cadherin+ pre-osteoblastic cells, a known niche component. By monitoring individual HSC behaviour using real-time imaging, we found that a portion of the homed HSCs underwent active division in the irradiated mice, coinciding with their expansion as measured by flow assay. Thus, in contrast to central marrow, the endosteum formed a special zone, which normally maintains HSCs but promotes their expansion in response to bone marrow damage.
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Author Information Reprints and permissions information is available at
www.nature.com/reprints. Correspondence and requests for materials should be
addressed to R.A.F. (rfeldman@umaryland.edu) and L.L. (lil@stowers-institute.org).
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