Nov/CCN3 regulates long-term repopulating activity of murine hematopoietic stem cells via integrin αvβ3 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-02-22

AUTHORS

Jun Ishihara, Terumasa Umemoto, Masayuki Yamato, Yoshiko Shiratsuchi, Satoshi Takaki, Brian G. Petrich, Hiromitsu Nakauchi, Koji Eto, Toshio Kitamura, Teruo Okano

ABSTRACT

Throughout life, hematopoietic stem cells (HSCs) sustain the blood cell supply through their capacities for self-renewal and multilineage differentiation. These processes are regulated within a specialized microenvironment termed the ‘niche’. Here, we show a novel mechanism for regulating HSC function that is mediated by nephroblastoma overexpressed (Nov/CCN3), a matricellular protein member of the CCN family. We found that Nov contributes to the maintenance of long-term repopulating (LTR) activity through association with integrin αvβ3 on HSCs. The resultant β3 integrin outside-in signaling is dependent on thrombopoietin (TPO), a crucial cytokine involved in HSC maintenance. TPO was required for Nov binding to integrin αvβ3, and stimulated Nov expression in HSCs. However, in the presence of IFNγ, a cytokine known to impair HSC function, not only was TPO-induced expression of Nov suppressed, but the LTR activity was conversely impaired by TPO-mediated ligation of integrin αvβ3 with exogenous ligands, including Nov, as well. Thus, Nov/integrin αvβ3-mediated maintenance of HSCs appears to be modulated by simultaneous stimulation by other cytokines. Our finding suggests that this system contributes to the regulation of HSCs within the bone marrow niche. More... »

PAGES

393-406

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-014-1534-x

DOI

http://dx.doi.org/10.1007/s12185-014-1534-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046188228

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24563081


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