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

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

SUBMITTER: Ishihara J 

PROVIDER: S-EPMC4412171 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature