Imperial College London
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DrJunIshihara

Faculty of Engineering, Department of Bioengineering

Lecturer
 
 
 
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Contact

 

j.ishihara Website CV

 
 
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Location

 

86 Woodlane London W12 0BZSir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Umemoto:2012:10.1182/blood-2011-02-335430,
author = {Umemoto, T and Yamato, M and Ishihara, J and Shiratsuchi, Y and Utsumi, M and Morita, Y and Tsukui, H and Terasawa, M and Shibata, T and Nishida, K and Kobayashi, Y and Petrich, BG and Nakauchi, H and Eto, K and Okano, T},
doi = {10.1182/blood-2011-02-335430},
journal = {Blood},
pages = {83--94},
title = {Integrin-αvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells},
url = {http://dx.doi.org/10.1182/blood-2011-02-335430},
volume = {119},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>Throughout life, one's blood supply depends on sustained division of hematopoietic stem cells (HSCs) for self-renewal and differentiation. Within the bone marrow microenvironment, an adhesion-dependent or -independent niche system regulates HSC function. Here we show that a novel adhesion-dependent mechanism via integrin-β3 signaling contributes to HSC maintenance. Specific ligation of β3-integrin on HSCs using an antibody or extracellular matrix protein prevented loss of long-term repopulating (LTR) activity during ex vivo culture. The actions required activation of αvβ3-integrin “inside-out” signaling, which is dependent on thrombopoietin (TPO), an essential cytokine for activation of dormant HSCs. Subsequent “outside-in” signaling via phosphorylation of Tyr747 in the β3-subunit cytoplasmic domain was indispensable for TPO-dependent, but not stem cell factor-dependent, LTR activity in HSCs in vivo. This was accompanied with enhanced expression of Vps72, Mll1, and Runx1, 3 factors known to be critical for maintaining HSC activity. Thus, our findings demonstrate a mechanistic link between β3-integrin and TPO in HSCs, which may contribute to maintenance of LTR activity in vivo as well as during ex vivo culture.</jats:p>
AU  - Umemoto,T
AU  - Yamato,M
AU  - Ishihara,J
AU  - Shiratsuchi,Y
AU  - Utsumi,M
AU  - Morita,Y
AU  - Tsukui,H
AU  - Terasawa,M
AU  - Shibata,T
AU  - Nishida,K
AU  - Kobayashi,Y
AU  - Petrich,BG
AU  - Nakauchi,H
AU  - Eto,K
AU  - Okano,T
DO  - 10.1182/blood-2011-02-335430
EP  - 94
PY  - 2012///
SN  - 0006-4971
SP  - 83
TI  - Integrin-αvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells
T2  - Blood
UR  - http://dx.doi.org/10.1182/blood-2011-02-335430
VL  - 119
ER  -
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