Detection of functional haematopoietic stem cell niche using real-time imaging.

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Title: Detection of functional haematopoietic stem cell niche using real-time imaging.
Authors: Xie, Yucai, Yin, Tong, Wiegraebe, Winfried, He, Xi C., Miller, Diana, Stark, Danny, Perko, Katherine, Alexander, Richard, Schwartz, Joel, Grindley, Justin C., Park, Jungeun, Haug, Jeff S., Wunderlich, Joshua P., Li, Hua, Zhang, Simon, Johnson, Teri, Feldman, Ricardo A., Li, Linheng
Source: Nature. 1/1/2009, Vol. 457 Issue 7225, p97-101. 5p. 2 Diagrams, 2 Graphs.
Subjects: Hematopoietic stem cells, Research methodology, Immunoassay, Green fluorescent protein, Stem cell transplantation, Medical imaging systems, Animal models in research
Abstract: Haematopoietic stem cell (HSC) niches, although proposed decades ago, have only recently been identified as separate osteoblastic and vascular microenvironments. 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–enhancer. 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. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Detection of functional haematopoietic stem cell niche using real-time imaging.
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  Data: <searchLink fieldCode="AR" term="%22Xie%2C+Yucai%22">Xie, Yucai</searchLink><br /><searchLink fieldCode="AR" term="%22Yin%2C+Tong%22">Yin, Tong</searchLink><br /><searchLink fieldCode="AR" term="%22Wiegraebe%2C+Winfried%22">Wiegraebe, Winfried</searchLink><br /><searchLink fieldCode="AR" term="%22He%2C+Xi+C%2E%22">He, Xi C.</searchLink><br /><searchLink fieldCode="AR" term="%22Miller%2C+Diana%22">Miller, Diana</searchLink><br /><searchLink fieldCode="AR" term="%22Stark%2C+Danny%22">Stark, Danny</searchLink><br /><searchLink fieldCode="AR" term="%22Perko%2C+Katherine%22">Perko, Katherine</searchLink><br /><searchLink fieldCode="AR" term="%22Alexander%2C+Richard%22">Alexander, Richard</searchLink><br /><searchLink fieldCode="AR" term="%22Schwartz%2C+Joel%22">Schwartz, Joel</searchLink><br /><searchLink fieldCode="AR" term="%22Grindley%2C+Justin+C%2E%22">Grindley, Justin C.</searchLink><br /><searchLink fieldCode="AR" term="%22Park%2C+Jungeun%22">Park, Jungeun</searchLink><br /><searchLink fieldCode="AR" term="%22Haug%2C+Jeff+S%2E%22">Haug, Jeff S.</searchLink><br /><searchLink fieldCode="AR" term="%22Wunderlich%2C+Joshua+P%2E%22">Wunderlich, Joshua P.</searchLink><br /><searchLink fieldCode="AR" term="%22Li%2C+Hua%22">Li, Hua</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Simon%22">Zhang, Simon</searchLink><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Teri%22">Johnson, Teri</searchLink><br /><searchLink fieldCode="AR" term="%22Feldman%2C+Ricardo+A%2E%22">Feldman, Ricardo A.</searchLink><br /><searchLink fieldCode="AR" term="%22Li%2C+Linheng%22">Li, Linheng</searchLink>
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  Data: Haematopoietic stem cell (HSC) niches, although proposed decades ago, have only recently been identified as separate osteoblastic and vascular microenvironments. 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–enhancer. 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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